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Bone Surface (bone + surface)
Selected AbstractsBuried alive: How osteoblasts become osteocytesDEVELOPMENTAL DYNAMICS, Issue 1 2006Tamara A. Franz-Odendaal Abstract During osteogenesis, osteoblasts lay down osteoid and transform into osteocytes embedded in mineralized bone matrix. Despite the fact that osteocytes are the most abundant cellular component of bone, little is known about the process of osteoblast-to-osteocyte transformation. What is known is that osteoblasts undergo a number of changes during this transformation, yet retain their connections to preosteoblasts and osteocytes. This review explores the osteoblast-to-osteocyte transformation during intramembranous ossification from both morphological and molecular perspectives. We investigate how these data support five schemes that describe how an osteoblast could become entrapped in the bone matrix (in mammals) and suggest one of the five scenarios that best fits as a model. Those osteoblasts on the bone surface that are destined for burial and destined to become osteocytes slow down matrix production compared to neighbouring osteoblasts, which continue to produce bone matrix. That is, cells that continue to produce matrix actively bury cells producing less or no new bone matrix (passive burial). We summarize which morphological and molecular changes could be used as characters (or markers) to follow the transformation process. Developmental Dynamics 235:176,190, 2006. © 2005 Wiley-Liss, Inc. [source] First missense mutation in the SOST gene causing sclerosteosis by loss of sclerostin function,HUMAN MUTATION, Issue 7 2010Elke Piters Abstract Sclerosteosis is a rare bone dysplasia characterized by greatly increased bone mass, especially of the long bones and the skull. Patients are tall, show facial asymmetry and often have syndactyly. Clinical complications are due to entrapment of cranial nerves. The disease is thought to be due to loss-of-function mutations in the SOST gene. The SOST gene product, sclerostin, is secreted by osteocytes and transported to the bone surface where it inhibits osteoblastic bone formation by antagonizing Wnt signaling. In a small Turkish family with sclerosteosis, we identified a missense mutation (c.499T>C; p.Cys167Arg) in exon 2 of the SOST gene. This type of mutation has not been previously reported and using different functional approaches, we show that it has a devastating effect on the biological function of sclerostin. The affected cysteine is the last cysteine residue of the cystine-knot motif and loss of this residue leads to retention of the mutant protein in the ER, possibly as a consequence of impaired folding. Together with a significant reduced ability to bind to LRP5 and inhibit Wnt signaling, the p.Cys167Arg mutation leads to a complete loss of function of sclerostin and thus to the characteristic sclerosteosis phenotype. © 2010 Wiley-Liss, Inc. [source] Two ,Medical' Cases from Medieval OsloINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 3 2002Per Holck Abstract An Erratum has been published for this article in International Journal of Osteoarchaeology 15(2) 2005, 153,154. More than one century of archaeological excavations in Oslo has brought several thousand medieval skeletons to light. Many of these are silent witnesses of the health conditions in the Norwegian capital during the 12th,16th centuries. This paper presents a description of two cases of special interest. One is a tibia that shows traces of cut marks due to a severe osteomyelitis; the other one has a depression in the bregma area which has perforated the skull roof and led to an inflammation of the bone surface. Both cases are probably proofs of deliberate medical care and skill of a high professional standard at that time. Copyright © 2002 John Wiley & Sons, Ltd. [source] The histological structure of the malleolar groove of the fibula in man: its direct bearing on the displacement of peroneal tendons and their surgical repairJOURNAL OF ANATOMY, Issue 2 2003T. Kumai Abstract The peroneal (fibularis) tendons are held in place within the malleolar groove by the superior peroneal retinaculum. If this is torn, the tendons can subluxate or dislocate. Understanding the anatomy of the region is important for treating these injuries when it becomes necessary to reconstruct the malleolar groove surgically. Serial transverse sections of the groove were cut from 10 dissecting room cadavers after routine histology processing. The structure of the malleolar groove differed significantly in its proximal and distal parts. Distally, the bone is convex and the shape of the groove is determined by a thick periosteal cushion of fibrocartilage that covers the bone surface. Proximally, the groove shape is determined by the bone itself, and the periosteum is thin and fibrous. The restriction of a periosteal fibrocartilage to the distal end suggests that it serves to adapt the shape of the malleolar groove to that of the tendons within it and thus promotes stress dissipation. Paradoxically, however, it increases the risk of damage to subluxated tendons, because these can be sliced longitudinally by a sharp ridge created from periosteal fibrocartilage when the retinaculum is torn. Our results suggest that if bone-block surgical procedures are used to reconstruct the malleolar groove, they are best restricted to its proximal part. [source] Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivoJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2010Anke J Roelofs Abstract Bisphosphonates are effective antiresorptive agents owing to their bone-targeting property and ability to inhibit osteoclasts. It remains unclear, however, whether any non-osteoclast cells are directly affected by these drugs in vivo. Two fluorescent risedronate analogues, carboxyfluorescein-labeled risedronate (FAM-RIS) and Alexa Fluor 647,labeled risedronate (AF647-RIS), were used to address this question. Twenty-four hours after injection into 3-month-old mice, fluorescent risedronate analogues were bound to bone surfaces. More detailed analysis revealed labeling of vascular channel walls within cortical bone. Furthermore, fluorescent risedronate analogues were present in osteocytic lacunae in close proximity to vascular channels and localized to the lacunae of newly embedded osteocytes close to the bone surface. Following injection into newborn rabbits, intracellular uptake of fluorescently labeled risedronate was detected in osteoclasts, and the active analogue FAM-RIS caused accumulation of unprenylated Rap1A in these cells. In addition, CD14high bone marrow monocytes showed relatively high levels of uptake of fluorescently labeled risedronate, which correlated with selective accumulation of unprenylated Rap1A in CD14+ cells, as well as osteoclasts, following treatment with risedronate in vivo. Similar results were obtained when either rabbit or human bone marrow cells were treated with fluorescent risedronate analogues in vitro. These findings suggest that the capacity of different cell types to endocytose bisphosphonate is a major determinant for the degree of cellular drug uptake in vitro as well as in vivo. In conclusion, this study shows that in addition to bone-resorbing osteoclasts, bisphosphonates may exert direct effects on bone marrow monocytes in vivo. © 2010 American Society for Bone and Mineral Research [source] Bone mineralization defects and vitamin D deficiency: Histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675,patientsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2010Matthias Priemel Abstract Parathyroid hormone (PTH) is only one measurable index of skeletal health, and we reasoned that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25-Hydroxyvitamin D [25(OH)D] level. A cohort from the northern European population with its known high prevalence of vitamin D deficiency therefore would be ideal to answer the latter question. We examined 675 iliac crest biopsies from male and female individuals, excluding all patients who showed any signs of secondary bone diseases at autopsy. Structural histomorphometric parameters, including osteoid indices, were quantified using the Osteomeasure System according to ASBMR standards, and serum 25(OH)D levels were measured for all patients. Statistical analysis was performed by Student's t test. The histologic results demonstrate an unexpected high prevalence of mineralization defects, that is, a pathologic increase in osteoid. Indeed, 36.15% of the analyzed patients presented with an osteoid surface per bone surface (OS/BS) of more than 20%. Based on the most conservative threshold that defines osteomalacia at the histomorphometric level with a pathologic increase in osteoid volume per bone volume (OV/BV) greater than 2% manifest mineralization defects were present in 25.63% of the patients. The latter were found independent of bone volume per trabecular volume (BV/TV) throughout all ages and affected both sexes equally. While we could not establish a minimum 25(OH)D level that was inevitably associated with mineralization defects, we did not find pathologic accumulation of osteoid in any patient with circulating 25(OH)D above 75,nmol/L. Our data demonstrate that pathologic mineralization defects of bone occur in patients with a serum 25(OH)D below 75,nmol/L and strongly argue that in conjunction with a sufficient calcium intake, the dose of vitamin D supplementation should ensure that circulating levels of 25(OH)D reach this minimum threshold (75,nmol/L or 30,ng/mL) to maintain skeletal health. © 2010 American Society for Bone and Mineral Research [source] Perspective: Quantifying Osteoblast and Osteocyte Apoptosis: Challenges and Rewards,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2007Robert L Jilka Abstract Since the initial demonstration of the phenomenon in murine and human bone sections ,10 yr ago, appreciation of the biologic significance of osteoblast apoptosis has contributed greatly not only to understanding the regulation of osteoblast number during physiologic bone remodeling, but also the pathogenesis of metabolic bone diseases and the pharmacology of some of the drugs used for their treatment. It is now appreciated that all major regulators of bone metabolism including bone morphogenetic proteins (BMPs), Wnts, other growth factors and cytokines, integrins, estrogens, androgens, glucocorticoids, PTH and PTH-related protein (PTHrP), immobilization, and the oxidative stress associated with aging contribute to the regulation of osteoblast and osteocyte life span by modulating apoptosis. Moreover, osteocyte apoptosis has emerged as an important regulator of remodeling on the bone surface and a critical determinant of bone strength, independently of bone mass. The detection of apoptotic osteoblasts in bone sections remains challenging because apoptosis represents only a tiny fraction of the life span of osteoblasts, not unlike a 6-mo -long terminal illness in the life of a 75-yr -old human. Importantly, the phenomenon is 50 times less common in human bone biopsies because human osteoblasts live longer and are fewer in number. Be that as it may, well-controlled assays of apoptosis can yield accurate and reproducible estimates of the prevalence of the event, particularly in rodents where there is an abundance of osteoblasts for inspection. In this perspective, we focus on the biological significance of the phenomenon for understanding basic bone biology and the pathogenesis and treatment of metabolic bone diseases and discuss limitations of existing techniques for quantifying osteoblast apoptosis in human biopsies and their methodologic pitfalls. [source] Remodeling and Vascular Spaces in BoneJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2007Erik Fink Eriksen Abstract In recent years, we have come to appreciate that the close association between bone and vasculature plays a pivotal role in the regulation of bone remodeling and fracture repair. In 2001, Hauge et al. characterized a specialized vascular structure, the bone remodeling compartment (BRC), and showed that the outer lining of this compartment was made up of flattened cells, displaying all the characteristics of lining cells in bone. A decrease in bone turnover leads to a decrease in surfaces covered with remodeling compartments, whereas increased turnover causes an increase. Immunoreactivity for all major osteotropic growth factors and cytokines including osteoprotegerin (OPG) and RANKL has been shown in the cells lining the BRC, which makes the BRC the structure of choice for coupling between resorption and formation. The secretion of these factors inside a confined space separated from the bone marrow would facilitate local regulation of the remodeling process without interference from growth factors secreted by blood cells in the marrow space. The BRC creates an environment where cells inside the structure are exposed to denuded bone, which may enable direct cellular interactions with integrins and other matrix factors known to regulate osteoclast/osteoblast activity. However, the denuded bone surface inside the BRC also constitutes an ideal environment for the seeding of bone metastases, known to have high affinity for bone matrix. Reduction in BRC space brought about by antiresorptive therapies such as bisphosphonates reduce the number of skeletal events in advanced cancer, whereas an increase in BRC space induced by remodeling activators like PTH may increase the bone metastatic burden. The BRC has only been characterized in detail in trabecular bone; there is, however, evidence that a similar structure may exist in cortical bone, but further characterization is needed. [source] Cancellous Bone Remodeling Occurs in Specialized Compartments Lined by Cells Expressing Osteoblastic MarkersJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2001Ellen M. Hauge Abstract We describe a sinus, referred to as a bone remodeling compartment (BRC), which is intimately associated with cancellous bone remodeling. The compartment is lined on its marrow side by flattened cells and on its osseous side by the remodeling bone surface, resembling a roof of flattened cells covering the bone surface. The flat marrow lining cells are in continuity with the bone lining cells at the margins of the BRC. We examined a large number of diagnostic bone biopsy specimens received during recent years in the department. Furthermore, 10 patients (8 women and 2 men, median age 56 [40,69] years) with the high turnover disease of primary hyperparathyroidism who were treated with parathyroidectomy and followed for 3 years were included in the histomorphometric study. Bone samples for the immuno-enzyme staining were obtained from an amputated extremity of child. The total cancellous bone surface covered by BRC decreases by 50% (p < 0.05) following normalization of turnover and is paralleled by a similar 50% decrease in remodeling surface (p < 0.05). The entire eroded surface and two-thirds of the osteoid surface are covered by a BRC. BRC-covered uncompleted walls are 30% (p < 0.05) thinner than those without a BRC. This indicates that the BRC is invariably associated with the early phases of bone remodeling, that is, bone resorption, whereas it closes during the late part of bone formation. Immuno-enzyme staining shows that the flat marrow lining cells are positive for alkaline phosphatase, osteocalcin, and osteonectin, suggesting that they are bone cells. The first step in cancellous bone remodeling is thought to be the lining cells digesting the unmineralized matrix membrane followed by their disappearance and the arrival of the bone multicellular unit (BMU). We suggest that the lining cell barrier persists during bone remodeling; that the old lining cells become the marrow lining cells, allowing bone resorption and bone formation to proceed under a common roof of lining cells; that, at the end of bone formation, new bone lining cells derived from the flattened osteoblasts replace the marrow lining cells thereby closing the BRC; and that the two layers of lining cells eventually becomes a single layer. The integrity of the osteocyte-lining cell system is reestablished by the new generation of lining cells. The BRC most likely serves multiple purposes, including efficient exchange of matrix constituents and minerals, routing, monitoring, or modulating bone cell recruitment, and possibly the anatomical basis for the coupling of bone remodeling. [source] Study of the Nonresorptive Phenotype of Osteoclast-like Cells from Patients with Malignant Osteopetrosis: A New Approach to Investigating PathogenesisJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2000Adrienne M. Flanagan Abstract Osteopetrosis manifests as failure of osteoclastic bone resorption. The cause of the disease lies either in the hematopoietic lineage or in the bone marrow stromal microenvironment. It has not been possible to define the cell type involved in the various forms of the human disease because of the inability to form human osteoclasts in vitro. Using the recently described method for generating human osteoclasts from peripheral blood in coculture with rat osteoblastic UMR 106 cells, we demonstrate that a defect lies in the mature osteoclast-like cells in four cases of this disease. Control and osteopetrotic cocultures generated large numbers of osteoclast-like cells (calcitonin and vitronectin receptor positive, and F-actin ring,positive cells) with similar morphology. Bone resorption did not occur in three of the four osteopetrotic cultures. In case 1, in which bone resorption was identified, the area of resorption was negligible compared with the number of osteoclast-like cells in the culture and was detected only by scanning electron microscopy. In contrast, up to 20% of the bone surface in controls was resorbed. The normal and osteopetrotic osteoclast-like cells had a similar phenotype except that two of the osteopetrotic cases did not express CD44 and two expressed CD44 weakly, whereas CD44 was strongly expressed in the controls. This study shows that it is possible to reproduce in vitro the pathological features of human osteopetrosis, and the assay provides a means of acquiring a greater understanding of the pathogenesis of human osteopetrosis. (J Bone Miner Res 2000;15:352,360) [source] Evaluation of bone surface registration applying a micro-needle arrayJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2007Kurt Schicho Abstract Aim: In this study we present and evaluated a new registration technology for the jaw-bone surface. It is based on a micromechatronic device for the generation of a "mechanical image" of the bone surface by means of an array of micro-needles that are penetrating the soft tissue until they touch the surface of the bone. This "mechanical impression image" is aligned with the CT data set. Material and Methods: Based on laboratory measurements on 10 specially prepared jawbone models we evaluate the accuracy of this new registration method. Results: Our measurements of the 10 specimens revealed a maximum overall location error of 0.97 mm (range: 0.35,0.97 mm). Conclusions: From the technical point of view the presented registration technology has the potential to improve the performance (i.e. accuracy and avoidance of errors) of the registration process for bony structures in selected applications of image-guided surgery. [source] Gentamicin used as an adjunct to GTRJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2003An experimental study in rats Abstract Objectives: To evaluate in a discriminating "capsule" model whether local application of gentamicin may have an added effect on bone formation produced by Bio-Oss® and guide tissue regeneration (GTR). Material and Methods: Thirty male 3-month-old Wistar rats were used. After elevation of muscle-periosteal flaps, a rigid hemispherical Teflon capsule, loosely packed with 0.025 g of Bio-Oss® impregnated with 2 mg/ml gentamicin sulfate (Garamycin®), was placed with its open part facing the lateral bone surface of the mandibular ramus (test) in one side of the jaw. A capsule filled only with Bio-Oss® (control) was placed on the contralateral side of the jaw. After healing periods of 1, 2 and 4 months, groups of 10 animals were sacrificed and the specimens were processed for histological examination. The volumes of (1) the space created by the capsule, (2) newly formed bone, (3) Bio-Oss® particles, (4) loose connective tissue, and (5) acellular space in the capsule were estimated by a point-counting technique in three to four histological sections of each specimen, taken by uniformly random sampling. Results: The histological evaluation showed limited but increasing bone fill in the capsules from 1 to 4 months in both the test and control sides. After 4 months, the newly formed bone occupied 11.9% (CV: 0.39) of the space created by the capsules at the test sides versus 13.2% (CV: 0.41) at the control sides. There was no statistical significant difference between test and control specimens at any observation time (p>0.05). Conclusion: It is concluded that local application of gentamicin has no added effect on bone formation when combined with Bio-Oss® and GTR. Zussamenfassung Gentamycin als Adjunktiv zur GTR genutzt. Eine experimentelle Studie bei Ratten Ziele:Überprüfung in einem "unterscheidenden" Kapselmodell, ob die lokale Applikation von Gentamycin einen zusätzlichen Effekt bei der Knochenbildung, die durch Bio-Oss® bei der GTR hervorgerufen wurde, hat. Material und Methoden: 30 männliche 3monatige Wistar-Ratten wurden genutzt. Nach der Elevation von Muskel-Periost-Lappen wurde eine rigide halbsphärische Teflonkapsel, die locker mit 0,025 g von Bio-Oss®, was mit Gentamycinsulfat 2mg/ml (Garamycin®) imprägniert war, auf einer Seite des Unterkieferramus (Test) so platziert, dass der offene Teil zur lateralen Knochenoberfläche gerichtet war. Eine Kapsel, die nur mit Bio-Oss gefüllt war (Kontrolle), wurde auf der kontralateralen Seite des Kiefers platziert. Nach der Heilungsperiode von 1, 2 und 4 Monaten wurden Gruppen von 10 Tieren getötet und die Proben für die histologische Überprüfung aufbereitet. Das Volumen von 1) dem Spalt, der durch die Kapsel geschaffen wurde, 2) dem neu gebildeten Knochen, 3) den Bio-Oss Partikeln, 4) dem lockeren Bindegewebe und 5) dem azellulären Spalt in der Kapsel wurden mit einer Punktzähltechnik in 3 bis 4 histologischen Schnitten von jeder Probe unter Nutzung einer allgemeinen Zufallsauswahl bestimmt. Ergebnisse: Die histologische Überprüfung zeigte eine limitierte aber zunehmende Knochenfüllung in der Kapsel vom 1. zum 4. Monat sowohl in der Test- als auch der Kontrollseite. Nach 4 Monaten besetzte der neu gebildete Knochen 11,9% (cv: 0,39) des von der Kapsel geschaffenen Spaltes bei den Testseiten verglichen mit 13,2% (cv: 0,41) bei den Kontrollseiten. Es gab keine statistisch signifikante Differenz zwischen Test- und Kontrollproben zu irgendeiner Beobachtungszeit (p>0,05). Schlussfolgerung: Es wird geschlossen, dass die lokale Applikation von Gentamycin keinen zusätzlichen Effekt auf die Knochenbildung hat, wenn eine Kombination mit Bio-Oss und der GTR erfolgt. Résumé La gentamycine utilisée en association à la GTR. Une étude expérimentale chez le rat Le but de cette étude a été d'évaluer si l'application locale de gentamycine dans un modèle de capsule discriminatoire pouvait avoir un effet additionnel bénéfique sur la formation osseuse produite par le Bio-Oss® et la GTR. Cette étude a eu recours à trente rats Wistar mâles de trois mois. Après l'élévation de lambeaux muscle-périoste, une capsule en téflon hémisphérique rigide, remplie de manière lâche avec 0,025 g de Bio-Oss® imprégnée avec 2mg/ml de sulfate de gentamycine (Garamycin®) a été placée avec sa face ouverte en regard de la surface osseuse latérale de la branche mandibulaire (test) d'un côté de la mâchoire. Une capsule remplie uniquement de Bio-Oss® (contrôle) a été placée dans le site contralatéral. Après des périodes de guérison de un, deux et quatre mois, des groupes de dix animaux ont été tués et les spécimens analysés histologiquement. Les volumes de 1) l'espace créé par la capsule, 2) l'os néoformé, 3) les particules de Bio-Oss®, 4) le tissu conjonctif lâche et 5) l'espace acellulaire dans la capsule ont été estimés par la technique de comptage par points dans trois à quatre coupes histologiques de chaque échantillon, pris de manière uniformément et randomisée. L'évaluation histologique a montré une augmentation limitée d'os dans les caspsules de un à quatre mois tant dans les sites tests que contrôles. Après quatre mois l'os néoformé occupait 11,9% (cv : 0,39) de l'espace créé par les capsules au niveau des sites tests vs 13,2% (cv : 0,41) au niveau des contrôles. Il n'y avait aucune différence statistique entre les échantillons tests et contrôles à aucun des temps d'observation (p>0,05). L'application locale de gentamycine n'aurait donc aucun effet sur la formation osseuse lorsqu'elle est placée avec le Bio-Oss® en association avec la GTR. [source] Osteogenesis by guided tissue regeneration and demineralized bone matrixJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 3 2003N. Mardas Abstract Aim:, To evaluate in a discriminating capsule model whether bone formation by guided tissue regeneration (GTR) may be influenced by concomitant implantation of demineralized bone matrix (DBM). Materials and Methods:, Thirty 4-month-old male albino rats of the Wistar strain were used in the study. Following surgical exposure of the mandibular ramus, a hemispherical, Teflon capsule (5.0 mm in diameter), loosely packed with a standardized amount of DBM, was placed with its open part facing the lateral bone surface of the ramus. At the contralateral side, an empty capsule was placed, serving as control. After healing periods of 15, 30, and 120 days, groups of 10 animals were sacrificed and 40,70 ,m thick undecalcified sections of the capsules were produced. In the sections, the cross-sectional areas of (1) the space created by the capsule, (2) newly formed bone, (3) DBM particles, (4) loose connective tissue as well as the (5) height of the capsules, and (6) that of the newly formed bone were measured. Results:, Increasing bone fill was observed in both test and control sites from 30 to 120 days. After 30 days of healing, the mean amount of bone was approx. 3% of the cross-sectional area of the capsules at the test sites while it was 8% in the control sites (p<0.05). However, no statistically significant differences were observed between the test (46%) and control (64%) sites after 120 days regarding any of the measured parameters (p>0.05). The newly formed bone in the DBM group at 120 days, on the other hand, appeared more dense than that in the control capsules. Conclusion:, DBM used as an adjunct to GTR did not provide any added effect on bone formation but increased the density of the newly formed bone. Zusammenfassung Ziel: Die Untersuchung in einem Kapselmodell, welches differenzieren kann, ob die Knochenbildung durch GTR durch die gleichzeitige Implantation von demineralisierter Knochenmatrix (DBM) beeinflusst werden könnte Material und Methoden: Dreißig männliche 4-Monate-alte Albinoratten des Wistar Stammes wurden in der Studie verwendet. Nach der chirurgischen Freilegung des Unterkieferastes wurde eine halbkugelförmige Teflonkapsel (5,0 mm Durchmesser), welche locker mit einer standardisierten Menge von DBM versehen war, wurde mit ihrer offenen Fläche auf die seitlichen Knochenfläche des Ramus gelegt. Auf der kontralateralen Seite diente eine leere Kapsel als Kontrolle. Nach Heilungsintervallen von 15, 30 und 120 Tagen wurden Gruppen von 10 Tieren geopfert und 40-70 ,m dicke nicht-entkalkte Schnitte der Kapseln wurden hergestellt. An den Schnitten wurde die Querschnittsfläche von: 1) der Fläche, die von der Kapsel geschaffen wurde, 2) dem neu gebildeten Knochen, 3) den DBM-Partikeln, 4) dem lockeren Bindegewebe gemessen, als auch 5) die Höhe der Kapseln und 6) des neu gebildeten Knochens bestimmt. Ergebnisse: Von Tag 30 zu Tag 120 wurde sowohl bei den Test- als auch bei den Kontrollstellen eine erhöhte Knochenauffüllung beobachtet. Nach 30 Tagen der Heilung betrug an den Teststellen die mittlere Knochenmenge ungefähr 3% der Querschnittsfläche der Kapseln, während sie an den Kontrollstellen 8% (p<0,05) betrug. Jedoch wurde nach 120 Tagen bei keinem der gemessenen Parameter eine statistisch signifikante Differenz zwischen den Test- (46%) und den Kontrollstellen (64%) beobachtet. Auf der anderen Seite erschien nach 120 Tagen in der DBM-Gruppe der neu gebildete Knochen dichter als in den Kontrollkapseln Schlussfolgerung: DBM welches als Zusatz bei der GTR verwendet wurde, lieferte keinen zusätzlichen Effekt bei der Knochenbildung, aber erhöhte die Dichte des neu gebildeten Knochens. Résumé Le but de cette étude a été d'évaluer dans un modèle de capsule discriminatoire si la formation osseuse par regénération tissulaire guidée (GTR) pouvait être influencée par l'implantation concomitante de matrice osseuse déminéralisée (DBM). Trente rats albinos mâles âgés de quatre mois de la souche Wistar ont été utilisés pour cette étude. A la suite de l'exposition chirurgicale de la branche montante mandibulaire, une capsule en téflon hémisphérique de 0,5 mm de diamètre remplie sans tassement avec une quantité standardisée de DBM a été placée avec sa partie ouverte contre la surface osseuse latérale de la branche. Du côté contralatéral, une capsule vide était placée servant de contrôle. Après des périodes de guérison de 15, 30 et 120 jours, des groupes de dix animaux ont été tués et des coupes non-décalcifiées de 40 à 70 ,m d'épaisseur des capsules ont été effectuées. Dans ces coupes, une aire sur coupe transversale contenant 1) l'espace créé par la capsule, 2) l'os néoformé, 3) des particules DBM, 4) du tissu conjonctif lâche; 5) la hauteur des capsules et 6) et celle de l'os néoformé ont été mesurés. Un comblement osseux de plus en plus important tant dans les sites contrôles que les sites tests a été constaté entre les jours 30 et 120. Après 30 jours de guérison, la quantité moyenne d'os formait approximativement 3% de l'aire de la coupe des capsules dans les sites tests tandis qu'elle était de 8% dans les sites contrôles (p<0,05). Cependant, aucune différence statistique n'a été observée entre les sites tests (46%) et les sites contrôles (64%) après 120 jours pour les paramètres mesurés (p>0,05). L'os néoformé dans le groupe DBM à 120 jours semblait plus dense que dans les capsules contrôles. Le DBM utilisé durant la GTR n'apportait aucun effet additionnel sur la formation osseuse mais augmentait cependant la densité du nouvel os formé. [source] Decreased oxidative stress and greater bone anabolism in the aged, when compared to the young, murine skeleton with parathyroid hormone administrationAGING CELL, Issue 5 2010Robert L. Jilka Summary Because of recent insights into the pathogenesis of age-related bone loss, we investigated whether intermittent parathyroid hormone (PTH) administration antagonizes the molecular mechanisms of the adverse effects of aging on bone. Parathyroid hormone produced a greater increase in vertebral trabecular bone mineral density and bone volume as well as a greater expansion of the endocortical bone surface in the femur of 26- when compared to 6 -month-old female C57BL/6 mice. Moreover, PTH increased trabecular connectivity in vertebrae, and the toughness of both vertebrae and femora in old, but not young, mice. Parathyroid hormone also increased the rate of bone formation and reduced osteoblast apoptosis to a greater extent in the old mice. Most strikingly, PTH reduced reactive oxygen species, p66Shc phosphorylation, and expression of the lipoxygenase Alox15, and it increased glutathione and stimulated Wnt signaling in bone of old mice. Parathyroid hormone also antagonized the effects of oxidative stress on p66Shc phosphorylation, Forkhead Box O transcriptional activity, osteoblast apoptosis, and Wnt signaling in vitro. In contrast, administration of the antioxidants N -acetyl cysteine or pegylated catalase reduced osteoblast progenitors and attenuated proliferation and Wnt signaling. These results suggest that PTH has a greater bone anabolic efficacy in old age because in addition to its other positive actions on bone formation, it antagonizes the age-associated increase in oxidative stress and its adverse effects on the birth and survival of osteoblasts. On the other hand, ordinary antioxidants cannot restore bone mass in old age because they slow remodeling and attenuate osteoblastogenesis by interfering with Wnt signaling. [source] Jaw bone remodeling at the invasion front of gingival squamous cell carcinomasJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2003Masahiro Ito Abstract Background:, It is still unknown how jaw bone remodeling occurs at actual invasion sites of oral squamous cell carcinomas. Since there is no other human carcinomas which make a direct invasion of the bone, gingival carcinomas are valuable examples. Methods:, Twelve surgical specimens of gingival squamous cell carcinoma were examined histopathologically and immunohistochemically for remodeling of bone and its surrounding tissue. Results:, Three types of bone interfaces with carcinomatous invasion were distinguished. These included areas with bone resorption, smooth bone surface and new bone formation. In the bone-resorption area, numerous osteoclasts were located along the bone surface, which was surrounded by myxoid stroma. The myxoid stroma was characterized by immunopositivity for heparan sulfate proteoglycan (HSPG), abundant vascularity and macrophagic infiltration. In the bone-formation area, rows of osteoblasts were aligned on the bone surface. The stroma around osteoblasts was also HSPG-immunopositive, poor in vascularity but rich in activated fibroblasts. In the smooth-bone area, the stroma showed an organizing phase of granulation tissue with slender fibroblasts and mature collagen fibers but with less vascularity and inflammatory infiltrates. Conclusion:, The results indicate that the stromal architecture, especially in terms of its inflammatory cellular, vascular and matrix compositions, is strictly regulated in the timing and site of jaw bone remodeling which is causes by carcinomatous invasion. [source] Early healing of flexor tendon insertion site injuries: Tunnel repair is mechanically and histologically inferior to surface repair in a canine modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2006Matthew J. Silva Abstract Orthopedic injuries often require surgical reattachment of tendon to bone. Tendon ends can be sutured to bone by direct apposition to the bone surface or by placement within a bone tunnel. Our objective was to compare early healing of a traditional surface versus a novel tunnel method for repair of the flexor digitorum profundus (FDP) tendon insertion site in a canine model. A total of 70 tendon,bone specimens were analyzed 0, 5, 10 or 21 days after injury and repair, using tensile and range of motion mechanical testing, histology and densitometry. Ultimate force (a measure of repair strength) did not differ between surface and tunnel repairs at day 0. Both repair types had reduced strength at 10 and 21 days compared to 0 days, indicative of deterioration of suture grasping strength (tendon softening). At 21 days, tendons repaired in a bone tunnel had 38% lower ultimate force compared to surface repairs (p,=,0.017). Histological findings were comparable between repair groups at 5 and 10 days but differed at 21 days, when we saw evidence of maturation of the tendon,bone interface in the surface repairs compared to an immature fibrous interface with no evidence of tendon,bone integration in the tunnel repairs. After accounting for bone removed by the tunnel, no difference in bone mineral density or trabecular bone volume existed between surface and tunnel repairs. If the results of our animal study extend to healing of the human FDP insertion, they indicate that FDP tendons should be reattached to the distal phalanx by suture to the cortical surface rather than suture in a bone tunnel. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Mechanical characteristics of the bone,graft,cement interface after impaction allograftingJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2005Hanspeter Frei Impaction allografting is an attractive procedure for the treatment of failed total hip replacements. The graft,cement,host bone interface after impaction allografting has not been characterized, although it is a potential site of subsidence for this type of revision total hip reconstruction. In six human cadaveric femurs, the cancellous bone was removed proximally and local diaphyseal lytic defects were simulated. After the impaction grafting procedure, the specimens were sectioned in 6 mm transverse sections and pushout tests were performed. From the adjacent sections the percentage cement contact of the PMMA cement with the endosteal bone surface was determined. The host bone interface mechanical properties varied significantly along the femur largely due to different interface morphologies. The apparent host bone interface shear strength was highest around the lesser trochanter and lowest around the tip of the stem. A significant positive correlation was found between the percentage cement contact and the apparent host bone interface shear strength (r2 = 0.52). The sections failed in 69% of the cases through a pure host bone interface failure without cement or allograft failure, 19% failed with local cement failure, and 12% with a local allograft failure. The apparent host bone interface strength was on average 89% lower than values reported for primary total hip replacements and were similar to cemented revisions proximally and lower distally. This study showed that cement penetration to the endosteal surface enhanced the host bone,graft interface. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Cambium cell stimulation from surgical release of the periosteumJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2003Timothy M. Simon An autograft of periosteal tissue containing cambium cells has potential to become chondrogenic or osteogenic depending on the regeneration repair strategies. The potential number of harvestable cambium cells diminishes with age. Other factors may be associated with a reduction in the number or variable yields of cambium cells including harvest technique, harvest site location, and the time interval from harvest to implantation. Attempts to increase the number of cambium cells have included improvements in harvesting and handling technique, and expansion of the cells in tissue culture. An ,in situ" stimulation and proliferation technique would offer the potential for increasing the number of cambium cells in a cost-effective manner for transplantation without the need for expansion in tissue culture. The hypothesis tested was that surgical release of the periosteum and its deep inner underlying cambium layer by sharply incising through the superficial periosteal fibrous layer down to and scoring the cortical bone surface would increase the number of cambium cells that could be harvested at a later time period. Two techniques for periosteal release were used to stimulate a proliferation of the underlying cambium layer and increase the cambium cells for harvest in skeletally mature goats: (1) sharply scoring all four-sides of the tissue test site perimeter, and (2) sharply scoring only two sides of the tissue test site. The two-sided and four-sided release scoring of the periosteum induced stimulatory responses in the number of cambium cells. In addition, a marked increase in mRNA expression for BMP-2 (p < 0.001) was observed within 24 h and remained elevated over baseline values for up to 96 h after this stimulation to the cambium layer. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] The role of macrophages in the periodontal regeneration using Emdogain® gelJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2008N. Fujishiro Background and Objective:, Emdogain® gel is clinically used as a periodontal regenerative material. However, the mechanism of the regeneration has not been completely elucidated. Although many studies have focused on the regenerative effect of Emdogain on connective tissue attachment and alveolar bone, the role of macrophages and the expression of growth factors remains unclear in the regeneration stimulated by Emdogain gel in vivo. The aim of this study was to investigate the effect of Emdogain gel on the expression of cytokines and growth factors by macrophages in vivo using a newly devised rat experimental periodontitis model. Material and Methods:, Rat experimental periodontitis was induced by elevating a full-thickness gingival flap and ligating silk threads around the first molars of the mandible. At 14 d after inducing experimental periodontitis, Emdogain gel or propylene glycol alginate was applied to the furcation area. The rats were killed 7 and 14 d after treatment with propylene glycol alginate or Emdogain gel. The expression of cytokines and growth factors, and the regeneration of periodontal tissue, were examined by histochemical and immunohistochemical methods. Results:, Fourteen days after the induction of periodontitis, the resorption of alveolar bone at furcation was observed and cytokines such as interleukin-1,, transforming growth factor-,1, receptor activator of nuclear factor-,B ligand, receptor activator of nuclear factor-,B and osteoprotegerin were found. In the Emdogain-treatment group, the formation of new acellular cementum and, more remarkably, recovery of the bone, were observed. The new bone formation ratio in the Emdogain treatment group was significantly higher than that of the propylene glycol alginate treatment group. Although the expression of cytokines such as interleukin-1,, transforming growth factor-,1, receptor activator of nuclear factor-,B ligand and receptor activator of nuclear factor-,B was very low, bone morphogenetic protein-2- and bone morphogenetic protein-4-expressing macrophages were observed close to the root, and bone morphogenetic protein-4-expressing macrophages were mainly observed close to the bone surface at the furcation in the Emdogain-treatment group. Conclusion:, These results suggest that wound-healing macrophages may express bone morphogenetic protein and play an important role in the regeneration of periodontal tissue at the furcation following the application of Emdogain gel. [source] Harvesting of intraoral autogenous block grafts from the chin and ramus region: Preliminary results with a variable square pulse Er:YAG laserLASERS IN SURGERY AND MEDICINE, Issue 5 2008Stefan Stübinger DDS Abstract Background and Objectives It was the aim of this pilot study to evaluate the feasibility, benefits and limitations of a variable square pulse (VSP) Er:YAG laser for harvesting intraoral bone grafts from either the chin or ramus region. Materials and Methods In 12 patients (5 female, 7 male) a VSP Er:YAG laser was used to harvest bone grafts either from the ramus (3) or the symphyseal area (9). For the osteotomies, the Er:YAG laser was applied with a pulse energy of 1,000 mJ, a pulse duration of 300 microseconds, and a frequency of 12 Hz (energy density 157 J/cm2). The spot size was 0.9 mm and the handpiece was kept at a distance of about 10 mm from the bone surface. Results There was no visible carbonization or osseous debris on the surface of the osteotomy gap. Damage of adjacent soft tissue structures by mechanical or thermal trauma was minimal. Cutting efficiency was excellent and the overall time required for the procedure was not increased. However, due to a free manual positioning of the laser beam in the non-contact mode, it was difficult to get a well defined osteotomy line without irregularities on the surface. Slight deviations of the original angulation of the laser beam led to considerable bone loss which restricted osteotomy of ramus grafts to three cases. Depth control was limited to visual inspection. Conclusion The bone ablation technique using a (VSP) Er:YAG laser yielded superior clinical results without impairment of wound healing and in comparison to other laser systems, no significant time loss occurred. Yet, the missing depth control and the necessity of carefully handling the laser beam position and its angulation limit the use of a (VSP) Er:YAG laser to regions where a safe and fixed guidance of the laser beam is feasible. Lesers Surg. Med. 40:312,318, 2008. © 2008 Wiley-Liss, Inc. [source] Bone histology of Silesaurus opolensisDzik, 2003 from the Late Triassic of PolandLETHAIA, Issue 2 2010UCJA FOSTOWICZ-FRELIK Fostowicz-Frelik, ,. & Sulej, T. 2009: Bone histology of Silesaurus opolensisDzik, 2003 from the Late Triassic of Poland. Lethaia, Vol. 43, pp. 137,148. The phylogenetic relationships of Silesaurus opolensis have been the subject of intense debate since its discovery. Silesaurus possesses some features characteristic of ornithischian dinosaurs, such as the presence of a beak at the front of the lower jaw, yet it lacks a number of important femoral and dental synapomorphies of Dinosauria. The microstructure of the long bones (femur, tibia and metatarsal) and ribs of this species reveals a relatively intensive rate of growth, comparable with that seen in small dinosaurs and the gracile crocodylomorph Terrestrisuchus. Cortical bone formed mainly by periosteal tissue with fibro-lamellar matrix (in older specimens parallel fibred) shows very little secondary remodelling and only in one specimen (large tibia ZPAL Ab III/1885) few lines of arrested growth are present in the outermost cortex. The vascularization is relatively dense, mainly longitudinal and ceases towards the periphery, forming almost avascular parallel fibred bone at the bone surface. This indicates maturation and significant decrease in the growth ratio in mature specimens of S. opolensis. The delicate trabeculae exhibit cores formed by the primary cancellous tissue lined with lamellar endosteal bone. The rather intense growth of S. opolensis implies a relatively high metabolic rate. Moreover, evidence from the fibro-lamellar tissue, predominant in the cortex, suggests that this kind of rapid bone deposition could be more typical of Archosauria than previously assumed, a prerequisite for the evolution of the very fast growth rates observed in large ornithischians, sauropods and large theropods. ,Archosauria, Bone histology, Dinosauriformes, Late Triassic, Silesaurus opolensis. [source] Histochemical evidence of osteoclastic degradation of extracellular matrix in osteolytic metastasis originating from human lung small carcinoma (SBC-5) cellsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 2 2006Minqi Li Abstract The aim of this study was to assess the dynamics of osteoclast migration and the degradation of unmineralized extracellular matrix in an osteolytic metastasis by examining a well-standardized lung cancer metastasis model of nude mice. SBC-5 human lung small carcinoma cells were injected into the left cardiac ventricle of 6-week-old BALB/c nu/nu mice under anesthesia. At 25,30 days after injection, the animals were sacrificed and their femora and/or tibiae were removed for histochemical analyses. Metastatic lesions were shown to occupy a considerable area extending from the metaphyses to the bone marrow region. Tartrate resistant acid phosphatase (TRAPase)-positive osteoclasts were found in association with an alkaline phosphatase (ALPase)-positive osteoblastic layer lining the bone surface, but could also be localized in the ALPase-negative stromal tissues that border the tumor nodules. These stromal tissues were markedly positive for osteopontin, and contained a significant number of TRAPase-positive osteoclasts expressing immunoreactivity for CD44. We thus speculated that, mediating its affinity for CD44, osteopontin may serve to facilitate osteoclastic migration after their formation associated with ALPase-positive osteoblasts. We next examined the localization of cathepsin K and matrix metallo-proteinase-9 (MMP-9) in osteoclasts. Osteoclasts adjacent to the bone surfaces were positive for both proteins, whereas those in the stromal tissues in the tumor nests showed only MMP-9 immunoreactivity. Immunoelectron microscopy disclosed the presence of MMP-9 in the Golgi apparatus and in vesicular structures at the baso-lateral cytoplasmic region of the osteoclasts found in the stromal tissue. MMP-9-positive vesicular structures also contained fragmented extracellular materials. Thus, osteoclasts appear to either select an optimized function, namely secreting proteolytic enzymes from ruffled borders during bone resorption, or recognize the surrounding extracellular matrix by mediating osteopontin/CD44 interaction, and internalize the extracellular matrices. Microsc. Res. Tech. 69:73,83, 2006. © 2006 Wiley-Liss, Inc. [source] Neurological aspects of osteopetrosisNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2003C. G. Steward The osteopetroses are caused by reduced activity of osteoclasts which results in defective remodelling of bone and increased bone density. They range from a devastating neurometabolic disease, through severe malignant infantile osteopetrosis (OP) to two more benign conditions principally affecting adults [autosomal dominant OP (ADO I and II)]. In many patients the disease is caused by defects in either the proton pump [the a3 subunit of vacuolar-type H(+)-ATPase, encoded by the gene variously termed ATP6i or TCIRG1] or the ClC-7 chloride channel (ClCN7 gene). These pumps are responsible for acidifying the bone surface beneath the osteoclast. Although generally thought of as bone diseases, the most serious consequences of the osteopetroses are seen in the nervous system. Cranial nerves, blood vessels and the spinal cord are compressed by either gradual occlusion or lack of growth of skull foramina. Most patients with OP have some degree of optic atrophy and many children with severe forms of autosomal recessive OP are rendered blind; optic decompression is frequently attempted to prevent the latter. Auditory, facial and trigeminal nerves may also be affected, and hydrocephalus can develop. Stenosis of both arterial supply (internal carotid and vertebral arteries) and venous drainage may occur. The least understood form of the disease is neuronopathic OP [OP and infantile neuroaxonal dystrophy, MIM (Mendelian inheritance in man) 600329] which causes rapid neurodegeneration and death within the first year. Although characterized by the finding of widespread axonal spheroids and accumulation of ceroid lipofuscin, the biochemical basis of this disease remains unknown. The neurological complications of this disease and other variants are presented in the context of the latest classification of the disease. [source] The Relationship Between Cephalic Scales and Bones in Lizards: A Preliminary Microtomographic Survey on Three Lacertid SpeciesTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 2 2010David Costantini Abstract In the last two decades, there has been a great deal of interest in the morphology and anatomy of the lizard skull in an ecological and evolutionary perspective. However, the relationship between variations in many key anatomical features remains largely unknown. Using microtomography and geometric morphometrics, we examined the relationship between bones and scales associated with the parietal foramen in the three lizards species most common in the Italian peninsula: Podarcis muralis, P. sicula, and Lacerta bilineata. The imprints of the scales are clearly recognizable on the outer bone surface, and this may suggest a structural interaction between these elements. The temporal osteoderms are visible in the larger males and in the larger females of L. bilineata, but they are absent in the smaller specimens of L. bilineata and in all Podarcis specimens. Two parallel rows of pterygoid teeth are present in all the specimens of L. bilineata and are absent in the smaller male of L. bilineata and in both Podarcis species. Cheek osteoderms occurred only in the largest specimens of our sample (i.e., large L. bilineata), being possibly related to hyperostotic processes and densitometric thresholds more than to phylogeny. Minor differences may be also associated with the form of the parietal foramen. In absolute terms the parietal foramen tends to be largest in L. bilineata but in relation to skull length the foramen tends to be larger in P. muralis. In this latter species the foramen is also more elongated. In all three species the fronto-parietal suture occupies a similar location relatively to the scale spatial organization. A shared allometric pattern shows that the main vault enlargement can be localised at the areas anterior to the fronto-parietal suture, providing further information on the possible morphogenetic dynamics associated with the interaction between scales and bones around this structure. Anat Rec, 2010. © 2009 Wiley-Liss, Inc. [source] Expression and localization of estrogen receptors , and , mRNA in medullary bone of laying hensANIMAL SCIENCE JOURNAL, Issue 2 2006Tomohiko IMAMURA ABSTRACT The aim of this study was to observe the expression and localization of estrogen receptor (ER) , and ER , mRNA in the medullary bone of laying hens. First, medullary bone, liver, kidney, and shell gland of the oviduct tissues were dissected from laying hens. Then, the total cellular RNA was isolated from each tissue specimen, and the ER , and ER , mRNA expression was observed using semiquantitative RT-PCR. Second, the localization of ER , mRNA in the medullary bone was detected with in situ hybridization using digoxigenin-11-UTP-labeled cRNA probes. As a result, the expression of ER , mRNA was higher than that of ER , mRNA in the medullary bone, liver, and shell gland of the oviduct from laying hens. In the kidney, ER , mRNA expression was lower than that of ER , mRNA. The expression pattern of ER , and ER , mRNA of the medullary bone was similar to that of the shell gland of the oviduct. Moreover, ER , mRNA was intensively expressed in osteoblasts on the medullary bone surface and bone marrow stromal cells but was not expressed in osteoclasts. These results suggest that in medullary bone, estrogen action may be regulated not by ER , but by ER ,. [source] Osteopontin deficiency impairs wear debris,induced osteolysis via regulation of cytokine secretion from murine macrophagesARTHRITIS & RHEUMATISM, Issue 5 2010Sadanori Shimizu Objective To investigate the molecular mechanisms underlying particle-induced osteolysis, we focused on osteopontin (OPN), a cytokine and cell-attachment protein that is associated with macrophage chemoattractant and osteoclast activation. Methods We compared OPN protein levels in human periprosthetic osteolysis tissues with those in osteoarthritis (OA) synovial tissues. To investigate the functions of OPN during particle-induced osteolysis in vivo, titanium particles were implanted onto the calvaria of OPN-deficient mice and their wild-type (WT) littermates. Mice were killed on day 10 and evaluated immunohistologically. The effects of OPN deficiency on the secretion of inflammatory cytokines were examined using cultured bone marrow,derived macrophages (BMMs). BMMs from OPN-deficient and WT mice were cultured with titanium particles for 12 hours, and the concentrations of inflammatory cytokines in the conditioned media were measured by enzyme-linked immunosorbent assay. Results Expression of OPN protein was enhanced in human periprosthetic osteolysis tissues as compared with OA synovial tissues. In the particle-induced model of osteolysis of the calvaria, bone resorption was significantly suppressed by OPN deficiency via inhibition of osteoclastogenesis, whereas an inflammatory reaction was observed regardless of the genotype. Results of immunostaining indicated that OPN protein was highly expressed in the membrane and bone surface at the area of bone resorption in WT mice. When BMMs were exposed to titanium particles, the concentration of proinflammatory cytokines, such as tumor necrosis factor ,, interleukin-1, (IL-1,), IL-1,, and IL-6, as well as chemotactic factors, such as monocyte chemoattractant protein 1 and macrophage inflammatory protein 1,, in the conditioned medium were significantly reduced by OPN deficiency. Whereas phagocytic activity of BMMs was not attenuated by OPN deficiency, phagocytosis-mediated NF-,B activation was impaired in OPN-deficient BMMs. These data indicated that OPN was implicated in the development of particle-induced osteolysis via the orchestration of pro-/antiinflammatory cytokines secreted from macrophages. Conclusion OPN plays critical roles in wear debris,induced osteolysis, suggesting that OPN is a candidate therapeutic target for periprosthetic osteolysis. [source] Calcium sensing and cell signaling processes in the local regulation of osteoclastic bone resorptionBIOLOGICAL REVIEWS, Issue 1 2004Mone Zaidi ABSTRACT The skeletal matrix in terrestrial vertebrates undergoes continual cycles of removal and replacement in the processes of bone growth, repair and remodeling. The osteoclast is uniquely important in bone resorption and thus is implicated in the pathogenesis of clinically important bone and joint diseases. Activated osteoclasts form a resorptive hemivacuole with the bone surface into which they release both acid and osteoclastic lysosomal hydrolases. This article reviews cell physiological studies of the local mechanisms that regulate the resorptive process. These used in vitro methods for the isolation, culture and direct study of the properties of neonatal rat osteoclasts. They demonstrated that both local microvascular agents and products of the bone resorptive process such as ambient Ca2+ could complement longer-range systemic regulatory mechanisms such as those that might be exerted through calcitonin (CT). Thus elevated extracellular [Ca2+], or applications of surrogate divalent cation agonists for Ca2+, inhibited bone resorptive activity and produced parallel increases in cytosolic [Ca2+], cell retraction and longer-term inhibition of enzyme release in isolated rat osteoclasts. These changes showed specificity, inactivation, and voltage-dependent properties that implicated a cell surface Ca2+ receptor (CaR) sensitive to millimolar extracellular [Ca2+]. Pharmacological, biophysical and immunochemical evidence implicated a ryanodine-receptor (RyR) type II isoform in this process and localized it to a unique, surface membrane site, with an outward-facing channel-forming domain. Such a surface RyR might function either directly or indirectly in the process of extracellular [Ca2+] sensing and in turn be modulated by cyclic adenosine diphosphate ribose (cADPr) produced by the ADP-ribosyl cyclase, CD38. The review finishes by speculating about possible detailed models for these transduction events and their possible interactions with other systemic mechanisms involved in Ca2+ homeostasis as well as the possible role of the RyR-based signaling mechanisms in longer-term cell regulatory processes. [source] Significance of primary stability for osseointegration of dental implantsCLINICAL ORAL IMPLANTS RESEARCH, Issue 3 2006Natalia Lioubavina-Hack Abstract Aim: To investigate the significance of the initial stability of dental implants for the establishment of osseointegration in an experimental capsule model for bone augmentation. Material and methods: Sixteen male rats were used in the study. In each rat, muscle-periosteal flaps were elevated on the lateral aspect of the mandibular ramus on both sides, resulting in exposure of the bone surface. Small perforations were then produced in the ramus. A rigid, hemispherical Teflon® capsule with a diameter of 6 mm and a height of 4 mm and with a hole in its middle portion, prepared to fit the circumference of an ITI® HC titanium implant of 2.8 mm in diameter, was fixed to the ramus using 4 mini-screws. On one side of the jaw, the implant was placed through the hole in such a way that its apex did not make contact with the mandibular ramus (test). This placement of the implant did not ensure primary stability. On the other side of the jaw, a similar implant was placed through the hole of the capsule in such a way that contact was made between the implant and the surface of the ramus (control). This provided primary stability of the implant. After placement of the implants, the soft tissues were repositioned over the capsules and sutured. After 1, 3, 6 and 9 months, four animals were sacrificed and subjected to histometric analysis. Results: The mean height of direct bone-to-implant contact of implants with primary stability was 38.8%, 52.9%, 64.6% and 81.3% of the implant length at 1, 3, 6 and 9 months, respectively. Of the bone adjacent to the implant surface, 28.1%, 28.9%, 52.6% and 69.6%, respectively, consisted of mineralized bone. At the test implants, no bone-to-implant contact was observed at any observation time or in any of these non-stabilized specimens. Conclusion: The findings of the present study indicate that primary implant stability is a prerequisite for successful osseointegration, and that implant instability results in fibrous encapsulation, thus confirming previously made clinical observations. [source] A nonsecosteroidal vitamin D receptor ligand with improved therapeutic window of bone efficacy over hypercalcemiaJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010Masahiko Sato Abstract Vitamin D3 analogues were shown to be beneficial for osteoporosis and other indications, but their narrow therapeutic window between efficacy and hypercalcemia has limited their clinical utility. A nonsecosteroidal, tissue-selective, orally bioavailable, vitamin D receptor (VDR) ligand was ascertained to be efficacious in bone while having modest calcemic effects in vivo. This compound (VDRM2) potently induced Retinoid X Receptor alpha (RXR)-VDR heterodimerization (EC50,=,7.1,±,1.6,nM) and induced osteocalcin promoter activity (EC50,=,1.9,±,1.6,nM). VDRM2 was less potent in inducing Ca2+ channel transient receptor potential cation channel, subfamily V, member 6 (TRPV6) expression (EC50,=,37,±,12,nM). VDRM2 then was evaluated in osteopenic ovariectomized (OVX) rats and shown to dose-dependently restore vertebral bone mineral density (BMD) from OVX to sham levels at 0.08,µg/kg per day. Hypercalcemia was observed at a dose of 4.6,µg/kg per day of VDRM2, suggesting a safety margin of 57 [90% confidence interval (CI) 35,91]. 1,,25-dihydroxyvitamin D3 [1,,25(OH)2D], ED71, and alfacalcidol restored BMD at 0.030, 0.0055, and 0.046,µg/kg per day, respectively, whereas hypercalcemia was observed at 0.22, 0.027, and 0.23,µg/kg per day, indicating a safety margin of 7.3, 4.9, and 5.0, respectively (90% CIs 4.1,13, 3.2,7.7, and 3.5,6.7, respectively). Histomorphometry showed that VDRM2 increased cortical bone area and stimulated the periosteal bone-formation rate relative to OVX at doses below the hypercalcemic dose. By contrast, ED71 increased the periosteal bone-formation rate only above the hypercalcemic dose. VDRM2 suppressed eroded surface on trabecular bone surfaces at normal serum calcium dosage levels, suggesting dual anabolic and antiresorptive activity. In summary, vitamin D analogues were more potent than VDRM2, but VDRM2 had a greater safety margin, suggesting possible therapeutic potential. © 2010 American Society for Bone and Mineral Research [source] Osteoblast Function Is Compromised at Sites of Focal Bone Erosion in Inflammatory Arthritis,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2009Nicole C Walsh PhD Abstract In rheumatoid arthritis (RA), synovial inflammation results in focal erosion of articular bone. Despite treatment attenuating inflammation, repair of erosions with adequate formation of new bone is uncommon in RA, suggesting that bone formation may be compromised at these sites. Dynamic bone histomorphometry was used in a murine model of RA to determine the impact of inflammation on osteoblast function within eroded arthritic bone. Bone formation rates at bone surfaces adjacent to inflammation were similar to those observed in nonarthritic bone; therefore, osteoblast activity is unlikely to compensate for the increased bone resorption at these sites. Within arthritic bone, the extent of actively mineralizing surface was reduced at bone surfaces adjacent to inflammation compared with bone surfaces adjacent to normal marrow. Consistent with the reduction in mineralized bone formation, there was a notable paucity of cells expressing the mid- to late stage osteoblast lineage marker alkaline phosphatase, despite a clear presence of cells expressing the early osteoblast lineage marker Runx2. In addition, several members of the Dickkopf and secreted Frizzled-related protein families of Wnt signaling antagonists were upregulated in arthritic synovial tissues, suggesting that inhibition of Wnt signaling could be one mechanism contributing to impaired osteoblast function within arthritic bone. Together, these data indicate that the presence of inflammation within arthritic bone impairs osteoblast capacity to form adequate mineralized bone, thus contributing to the net loss of bone and failure of bone repair at sites of focal bone erosion in RA. [source] | ||||||||||||||||