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Long Bones (long + bone)
Terms modified by Long Bones Selected AbstractsEnhanced Bone Bonding of the Hydroxyapatite/,-Tricalcium Phosphate Composite by Electrical Polarization in Rabbit Long BoneARTIFICIAL ORGANS, Issue 6 2010Hideki Sagawa Abstract A review of the osteogenic cell activity and new bone growth in the regions bordering negatively charged surfaces of polarized Hydroxyapatite/,-tricalcium phosphate (HA/TCP) composites implanted in the long bone in rabbits was conducted. Polarized and non-polarized HA/TCP specimens were implanted into the right and left femoral condyle, respectively (each n = 10). After 3 and 6 weeks, five rabbits were sacrificed in each group, and histological analysis was administered. Large cuboidal-shaped osteoblastic cells were predominantly observed lining the newly formed bone on the negatively charged surface (N-surface) in the polarized HA/TCP implants. The TRAP-positive multinucleated cells were observed extensively in the newly formed bone on the N-surfaces compared with the 0-surface and adhered directly to the HA/TCP composite. The bone area (B.Ar) value, newly formed bone area contacting the implant, and contact length (C.Le) value, percentage length of newly formed bone directly attaching to the implant, on both the 0- and N-surface increased significantly with time in each group. Both the B.Ar and C.Le value on the N-surface were significantly greater than those on the 0-surface after 3 and 6 weeks. The number of TRAP-positive cells/total length value on the N-surface was significantly greater than that on the 0-surface after 3 and 6 weeks postoperatively. It is hypothesized that electrical charge acquired by electrical polarization treatment may modify the biochemical and biophysical processes of the osteogenic cells, resulting in enhanced new bone formation and direct bonding between the recipient bone and implants. [source] Thyroid-Stimulating Hormone Restores Bone Volume, Microarchitecture, and Strength in Aged Ovariectomized Rats*,,§JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007T Kuber Sampath PhD Abstract We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. Introduction: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. Materials and Methods: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8,16 wk. Long bones were subjected to ,CT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. Results: In the prevention mode, low doses (0.1 and 0.3 ,g) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 ,g TSH had increased BMD (10,11%), trabecular bone volume (100,130%), trabecular number (25,40%), trabecular thickness (45,60%), cortical thickness (5,16%), mineral apposition and bone formation rate (200,300%), and enhanced mechanical strength of the femur (51,60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. Conclusions: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling. [source] Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 (rhBMP-2) and a synthetic polymerJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2002Narumichi Murakami Abstract To develop a new technology that enhances the regeneration potential of bone and the repair of large intercalated defects in long bone, recombinant human bone morphogenetic protein-2 (BMP-2; 20 ,g or 40 ,g) was mixed in a polymer gel (poly-lactic acid-polyethyleneglycol block copolymer; PLA-PEG; 200 mg) and incorporated into titanium fiber-mesh cylinders. Three 5-mm cylinders were placed end-to-end to fill a 15-mm defect created in the humeri of adult rabbits and were stabilized by an intramedullary rod. In controls, the titanium fiber-mesh cylinders were combined with PLA-PEG in the absence of BMP. Six weeks after implantation, new bone had formed on the surface of the implant and had bridged the defect. All of the defects (5/5) treated by cylinders containing 120 ,g (40 ,g × 3) of BMP were repaired completely. New bone formation was also found inside the pores of the cylinders. The defect was not repaired in the control animals. These results demonstrate that these new composite implants fabricated by combining rhBMP, synthetic degradable polymers and compatible biomaterials enhance the regeneration potential of bone. Thus, it is possible that large skeletal defects can be repaired using this prosthesis in lieu of autogenous bone graft. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 169,174, 2002 [source] Mechanical Strain Stimulates Osteoblast Proliferation Through the Estrogen Receptor in Males as Well as FemalesJOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2000E. Damien Abstract Mechanical strain, testosterone, and estrogen all stimulate proliferation of primary cultures of male rat long bone (LOB)-derived osteoblast-like cells as determined by [3H]thymidine incorporation. The maximum proliferative effect of a single period of mechanical strain (3400 ,,, 1 Hz, and 600 cycles) is additional to that of testosterone (10,8 M) or estrogen (10,8 M). The cells' proliferative response to strain is abolished both by concentrations of tamoxifen that cause proliferation (10,8 M) and by those that have no effect (10,6 M). Strain-related proliferation also is reduced by the estrogen antagonist ICI 182,780 (10,8 M) but is unaffected by the androgen receptor antagonist hydroxyflutamide (10,7 M). Tamoxifen, ICI 182,780, and the aromatase inhibitor 4-dihydroandrostenedione, at concentrations that have no effect on basal proliferation, significantly reduce the proliferative effect of the aromatizable androgen testosterone but not that of the nonaromatizable androgen 5,-dihydrotestosterone. Hydroxyflutamide, at a concentration that has no effect on basal proliferation (10,7 M), eliminates the proliferative effect of 5,-dihydro-testosterone but had no significant effect on that caused by testosterone. Proliferation associated with strain is blocked by neutralizing antibody to insulin-like growth factor II (IGF-II) but not by antibody to IGF-I. Proliferation associated with testosterone is blocked by neutralizing antibody to IGF-I but is unaffected by antibody to IGF-II. These data suggest that in rat osteoblast-like cells from males, as from females, strain-related proliferation is mediated through the estrogen receptor (ER) in a manner that does not compete with estrogen but that can be blocked by ER modulators. Proliferation associated with testosterone appears to follow its aromatization to estrogen and is mediated through the ER, whereas proliferation associated with 5,-dihydrotestosterone is mediated by the androgen receptor. Strain-related proliferation in males, as in females, is mediated by IGF-II, whereas proliferation associated with estrogen and testosterone is mediated by IGF-I. [source] Differential gene expression analysis using paraffin-embedded tissues after laser microdissectionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2003Joung-Ok Kim Abstract Recent advances in laser microdissection allow for precise removal of pure cell populations from morphologically preserved tissue sections. However, RNA from paraffin-embedded samples is usually degraded during microdissection. The purpose of this study is to determine the optimal fixative for RNA extractions from laser microdissected paraffin-embedded samples. The integrity of RNA was evaluated with the intactness of 18S and 28S ribosomal RNA by electrophoresis and by the length of individual gene transcripts using RT-PCR. The various fixatives were methacarn (a combination of methanol, chloroform, and acetic acid) and several concentrations of ethanol and isopropanol. Methacarn was the optimal fixative for RNA preservation in paraffin-embedded tissues, which included liver, lung, kidney, muscle, and limb. Based on RT-PCR analysis, methacarn fixed samples exhibited the expected RNA sizes for individual genes such as glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and bone-related genes (e.g., alkaline phosphatase and osteonectin). The laser microdissection technique with methacarn fixation was then applied to analyze the differential gene expression between hypertrophic and proliferative chondrocytes in the growth plate of long bone. The expression of type X collagen (ColX,1), a specific gene for hypertrophic chondrocytes, was only observed in hypertrophic chondrocytes, while type II collagen (Col2,1) was observed more broadly in the growth plate as anticipated. Thus, combining laser microdissection with methacarn fixation facilitates the examination of differentially expressed genes from various tissues. © 2003 Wiley-Liss, Inc. [source] Testing Anatomical Methods for Stature Estimation on Individuals from the W. M. Bass Donated Skeletal CollectionJOURNAL OF FORENSIC SCIENCES, Issue 4 2009Heli Maijanen M.A. Abstract:, This study compared eight versions of the anatomical method for stature estimation on a white male sample (n = 34) from the W. M. Bass Donated Skeletal Collection. The aim was to evaluate errors in the estimates and to discuss how useful the methods are in forensic context. The average error estimating living stature was less than 1 cm for six of the methods. The correlations between the estimates were high (r = 0.982,0.999). In practice, differences between the versions as well as those between long bone-based equations and anatomical methods were small. Anatomical method is nevertheless more accurate than long bone regressions when individuals with atypical body proportions are examined. [source] Effect of cell-based VEGF gene therapy on healing of a segmental bone defectJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2009Ru Li Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating/affecting proliferation, survival, and activity of skeletal cells. Using a cell-based method of gene transfer, without viral vector, 5.0,×,106 fibroblasts transfected with VEGF were delivered to a 10-mm bone defect in rabbit tibiae (Group 1) (n,=,9); control groups were treated with fibroblasts (Group 2) (n,=,7), or saline (Group 3) (n,=,7) only. After 12 weeks, eight tibial fractures healed in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group 1 had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (p,<,0.05). These results indicate that the cell-based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:8,14, 2009 [source] Regulation of embryonic endochondral ossification by Smurf2JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2008Qiuqian Wu Abstract Smurf2 is an E3 ubiquitin ligase that targets TGF-, receptor activated Smad2 and Smad3 for the proteasome in primary articular chondrocytes, thus stimulating their hypertrophic differentiation. Comparatively, how Smurf2 functions in growth plate chondrocytes in a developing long bone is an open question. In this study, we measured the mRNA levels of endogenous Smurf2 and type X collagen in chick growth plate at different embryonic stages to monitor the correlation between the level of Smurf2 expression and chondrocyte maturational stage. We found that high levels of Smurf2 were associated with the differentiative and proliferative stages, while Smurf2 levels were thereafter decreased as the chondrocytes matured toward hypertrophy. In addition, we injected Smurf2 -RCAS into chick wing buds at HH stage 20,23 and examined how the ectopic overexpression of Smurf2 in condensing chondrogenic mesenchyme affects the subsequent process of chondrocyte maturation and ossification during embryonic development. Histological analysis showed that overexpression of Smurf2 in a developing wing bud accelerated chondrocyte maturation and endochondral ossification, which may result from a decrease in TGF-, signaling in the infected chondrocytes with Smurf2 -RCAS. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:704,712, 2008 [source] Signalling molecules and growth factors for tissue engineering of cartilage,what can we learn from the growth plate?,JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 6 2009Christoph Brochhausen Abstract Modern tissue engineering concepts integrate cells, scaffolds, signalling molecules and growth factors. For the purposes of regenerative medicine, fetal development is of great interest because it is widely accepted that regeneration recapitulates in part developmental processes. In tissue engineering of cartilage the growth plate of the long bone represents an interesting, well-organized developmental structure with a spatial distribution of chondrocytes in different proliferation and differentiation stages, embedded in a scaffold of extracellular matrix components. The proliferation and differentiation of these chondrocytes is regulated by various hormonal and paracrine factors. Thus, members of the TGF, superfamily, the parathyroid hormone-related peptide,Indian hedgehog loop and a number of transcription factors, such as Sox and Runx, are involved in the regulation of chondrocyte proliferation and differentiation. Furthermore, adhesion molecules, homeobox genes, metalloproteinases and prostaglandins play a role in the complex regulation mechanisms. The present paper summarizes the morphological organization of the growth plate and provides a short but not exhaustive overview of the regulation of growth plate development, giving interesting insights for tissue engineering of cartilage. Copyright © 2009 John Wiley & Sons, Ltd. [source] Spatiotemporal Localization of VEGF-A Isoforms in the Mouse Postnatal Growth PlateTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2008Kristin D. Evans Abstract Vascular endothelial growth factor (VEGF) is implicated as a key angiogenic factor in the development of endochondral long bone. Several studies have evaluated the role of VEGF in prenatal endochondral bone development, but few have evaluated VEGF postnatally. Growth plates from mice at postnatal ages 14 (P14), 35 (P35), 49 (P49), and 77 (P77) days were examined for differential expression of the primary VEGF-A mRNA isoforms: VEGF 120, VEGF 164, and VEGF 188. VEGF 120 isoform expression was stable across all ages, whereas VEGF 164 had significantly less expression at P35 and P49 and VEGF l88 expression increased with increasing age. The proportion of transcript isoforms expressed at a given age also changed with VEGF 120 being expressed more highly at P35 and P49 than the other two isoforms. Changes in VEGF mRNA isoforms across cell types within the growth plate were assessed by Percoll fractionation of growth plate cells at age P28. Cells of the proliferative and early hypertrophic regions had significantly higher total VEGF mRNA expression relative to the resting and late hypertrophic regions. VEGF protein expression assessed by immunohistochemistry showed variable expression patterns with increasing postnatal age. In contrast, FLK-1 (VEGF Receptor-2) expression was restricted to the hypertrophic region. These results indicate that VEGF continues to play a significant role in endochondral bone development throughout the entire growth phase of postnatal bone development. Anat Rec, 291:6,13, 2007. © 2007 Wiley-Liss, Inc. [source] Development of Galanin-Containing Nerve Fibres in Rat TibiaANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2 2009M. Gajda Summary Galanin exerts tonic inhibition of nociceptive input to the central nervous system. Recently, this peptide was demonstrated in several neuronal and non-neuronal structures in bones and joints. In this study, the time of appearance and topographic localization of galanin-containing nerve fibres in bone were studied in rats from gestational day 16 (GD16) to postnatal day 21 (PD21). The tibia was chosen as a model of developing long bone and indirect immunofluorescence combined with confocal laser scanning microscopy was used to identify galanin-immunoreactive (GAL-IR) nerve fibres. The earliest, sparse GAL-IR fibres were observed on GD21 in the perichondrium of both epiphyses and in the periosteum of the diaphysis. From PD1 onwards, GAL-IR fibres were also seen in the bone marrow cavity and in the region of the inter-condylar eminence of the knee joint. Intramedullary GAL-IR fibres in proximal and distal metaphyses appeared around PD1. Some of them accompanied blood vessels, although free fibres were also seen. GAL-IR fibres located in the cartilage canals of both epiphyses were observed from PD7, in the secondary ossification centres from PD10 and in the bone marrow of both epiphyses from PD14. The time course and localization of galanin-containing nerve fibres resemble the development of substance P- and CGRP-expressing nerve fibres, thus suggesting their sensory origin. [source] Enhanced Bone Bonding of the Hydroxyapatite/,-Tricalcium Phosphate Composite by Electrical Polarization in Rabbit Long BoneARTIFICIAL ORGANS, Issue 6 2010Hideki Sagawa Abstract A review of the osteogenic cell activity and new bone growth in the regions bordering negatively charged surfaces of polarized Hydroxyapatite/,-tricalcium phosphate (HA/TCP) composites implanted in the long bone in rabbits was conducted. Polarized and non-polarized HA/TCP specimens were implanted into the right and left femoral condyle, respectively (each n = 10). After 3 and 6 weeks, five rabbits were sacrificed in each group, and histological analysis was administered. Large cuboidal-shaped osteoblastic cells were predominantly observed lining the newly formed bone on the negatively charged surface (N-surface) in the polarized HA/TCP implants. The TRAP-positive multinucleated cells were observed extensively in the newly formed bone on the N-surfaces compared with the 0-surface and adhered directly to the HA/TCP composite. The bone area (B.Ar) value, newly formed bone area contacting the implant, and contact length (C.Le) value, percentage length of newly formed bone directly attaching to the implant, on both the 0- and N-surface increased significantly with time in each group. Both the B.Ar and C.Le value on the N-surface were significantly greater than those on the 0-surface after 3 and 6 weeks. The number of TRAP-positive cells/total length value on the N-surface was significantly greater than that on the 0-surface after 3 and 6 weeks postoperatively. It is hypothesized that electrical charge acquired by electrical polarization treatment may modify the biochemical and biophysical processes of the osteogenic cells, resulting in enhanced new bone formation and direct bonding between the recipient bone and implants. [source] Osteosarcoma metastatic to adrenal gland diagnosed by fine-needle aspirationDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2005Noman H. Siddiqui M.D. Abstract Osteosarcoma, a primary malignant tumor of the long bones, frequently metastasizes to the lungs. We report an unusual case of osteosarcoma metastatic to the right adrenal gland in a 37-yr-old male who presented 8 yr after remission with an adrenal mass. A preoperative diagnosis was made by fine-needle aspiration (FNA) biopsy. FNA biopsy revealed pleomorphic oval cells with prominent nucleoli, spindle cells, and giant tumor cells. Diagnostic osteoid was readily seen on smears and was also detected by polarization of cell-block section. Immunocytochemical stains revealed positivity of tumor cells for vimentin and osteonectin. Cytokeratin stains were negative. The cytologic diagnosis of metastatic Osteosarcoma was made, which was later confirmed upon resection of tumor by histology. Although the role of FNA in the diagnosis of primary bone tumors, including osteogenic sarcoma (OGS), remains controversial, this case, however, demonstrates the value of FNA biopsy combined with immunocytochemistry performed on the aspirated material in diagnosing osteosarcoma from an unusual location such as the adrenal gland. Diagn. Cytopathol. 2005;33:201,204. © 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] Heterozygous SOX9 Mutations Allowing for Residual DNA-binding and Transcriptional Activation Lead to the Acampomelic Variant of Campomelic Dysplasia,HUMAN MUTATION, Issue 6 2010Alex Staffler Abstract Campomelic dysplasia is a malformation syndrome with multiple symptoms including characteristic shortness and bowing of the long bones (campomelia). CD, often lethal due to airway malformations, is caused by heterozygous mutations in SOX9, an SRY-related gene regulating testis and chondrocyte development including expression of many cartilage genes such as type II collagen. Male to female sex reversal occurs in the majority of affected individuals with an XY karyotype. A mild form without campomelia exists, in which sex-reversal may be also absent. We report here two novel SOX9 missense mutations in a male (c.495C>G; p.His165Gln) and a female (c.337A>G; p.Met113Val) within the DNA-binding domain leading to non-lethal acampomelic CD. Functional analyses of mutant proteins demonstrate residual DNA-binding and transactivation of SOX9-regulated genes. Combining our data and reports from the literature we postulate a genotype-phenotype correlation: SOX9 mutations allowing for residual function lead to a mild form of CD in which campomelia and sex reversal may be absent. © 2010 Wiley-Liss, Inc. [source] Residual rickets or osteomalacia: a case dating from the 16,18th centuries from Krosno Odrza,skie, PolandINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2009E. Haduch Abstract A skeleton from a 16,18th century burial site in Krosno Odrza,skie, Poland, was examined using classical morphological, metric and macroscopic palaeopathological observations, as well as radiography and tomography of the skull and long bones. A wide variety of the observed bone deformations probably occurred as a consequence of past rickets and/or osteomalacia, whose primary cause may also have been chronic renal failure. Preservation of the bones enables a discussion of the cause of such pathological changes. The subject under study appears to be a very interesting example of an individual whose skeleton shows advanced pathological alterations associated with the subject's vitamin D deficiency, overall health conditions and relatively long lifespan. Copyright © 2008 John Wiley & Sons, Ltd. [source] Necropoli of Pill'e Matta Quartucciu (Cagliari, Sardinia): wild bee and solitary wasp activity and bone diagenetic factorsINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 3 2009E. Pittoni Abstract During the excavation at the necropolis and the laboratory studies, a variety of damage was found in the human bone remains. This damage included round holes, irregular bone destruction and irregular etching. This can be found especially in the skulls and in the long bones, and sometimes in the vertebrae and on the hands and feet. The exceptionality of this demanded meticulous study in order to define whether it was a diagenetic phenomenon of biological origin. Further studies revealed that the damage to the bones was produced by three kinds of Hymenoptera that build galleries: one of these belongs to the Sphecidae family, the other two to the Halictidae family. During the excavation of a grave it had been observed that a Halictidae had invaded the burial context and consequently contributed to the taphonomic and diagenetic process. The laboratory activities were directed towards the measurement of the damage to the human bone remains in 45 tombs. A histogram shows that the holes are not the result of accidental lesions, and the more frequent percentage values show similarities with the dimensions of holes built by the insects. The observations and the results of the study at the archaeological site enabled me to establish how significant the role of the insects had been, in particular of the Hymenoptera, in modifying the condition of the bone remains. Copyright © 2008 John Wiley & Sons, Ltd. [source] Sexual dimorphism in limb bones of ibex (Capra ibex L.): mixture analysis applied to modern and fossil dataINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2007H. Fernández Abstract Estimating sex ratios of fossil bone assemblages is an important step in the determination of demographic profiles, which are essential for understanding the palaeobiology and palaeoethology of any particular species, as well as its exploitation patterns by humans. This is especially true for ibex (Capra ibex), which was a main source of food for hominids during Pleistocene times. Classical methods for determining sexual dimorphism and sex ratio, such as analyses using uni- and bivariate plots, are based on an arbitrary fixing of limits between sexes. Here we use a more robust statistical method termed mixture analysis (MA) to determine the sex of postcranial remains (long bones, metapodials and tarsals) from ibex. For the first time, we apply MA to both a modern and a fossil sample of one species, by using metric data taken from (i) a collection of present-day ibex skeletons and (ii) a Palaeolithic sample of the same species. Our results clearly show that the forelimb (humerus and radius) is more dimorphic than the hindlimb (femur and tibia) and is therefore better suited for sexing ibex. It also appears that metapodials should be used carefully for estimating sex ratios. On the basis of these results, we propose a classification of bone measurements that are more or less reliable for sexing ibex. The results of MA applied to the ibex fossil bones from the Upper Palaeolithic site of the Observatoire (Monaco) lead us to the conclusion that this assemblage consists of a majority of males. The quantitative estimations calculated by the MA make it possible to compare the size of Pleistocene and modern ibex for the whole set of variables used in this study. Copyright © 2006 John Wiley & Sons, Ltd. [source] A pre-Columbian case of congenital syphilis from Anatolia (Nicaea, 13th century AD)INTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 1 2006Y. S. ErdalArticle first published online: 16 AUG 200 Abstract In this study, the skeleton of an approximately 15-year-old child, dating back to the Late Byzantine period (13th century AD) is examined with the aim of determining where this specimen fits in the continuing arguments on the origins of syphilis. It was unearthed during an excavation at an amphitheatre in Nicaea dating to the Roman period. The Nicaea specimen displays common symptoms found in the majority of people with congenital syphilis such as Hutchinson's incisor, mulberry molar, darkened enamel, radial scar on frontal bone, sabre tibia, syphilitic dactylitis, and gummatous and non-gummatous osteomyelitis on almost every post-cranial bone. Because of the sub-periosteal new bone formation, the medullary spaces in some long bones are narrowed or completely obliterated. These lesions, which were observed via macroscopic and radiological examination, reflect the late stages of congenital syphilis. The specimen, when examined together with increasing numbers of other finds from the Old World, contributes to the argument that venereal syphilis did exist in the Old World before 1493, and brings forward the need to revise the Columbian hypothesis, which maintains that syphilis is a new disease carried to the Old World from the New World by Columbus' crew. Copyright © 2005 John Wiley & Sons, Ltd. [source] A possible case of spondyloarthropathy in a prehistoric Japanese skeletonINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 3 2005K. Inoue Abstract Palaeopathology helps to define the migration of past diseases. Genetic and environmental factors play a role in the development of spondyloarthropathy (SpA). We report skeletal remains with SpA from the Jomon period in Japan. The skeleton is of a female who died at a young adult age. The skeleton had characteristic features seen in SpA as follows: (1) polyarticular arthritis; (2) erosions accompanying some bone formation; (3) enthesial ossification; and (4) periostitis in lower long bones. The findings suggest that SpA was present in prehistoric Japan before contact with European civilisation, and the present example of SpA is the oldest in Asia and the Old World. Copyright © 2004 John Wiley & Sons, Ltd. [source] Trauma in the city of Kerma: ancient versus modern injury patternsINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 1 2004M. Judd Abstract Injuries, whether accidental or intentional, have incapacitated humans and their primordial ancestors throughout time, although the injury mechanisms have become increasingly more technologically sophisticated. Interpretation of injury aetiology among past peoples is challenging, and often impossible, however, clinical research from developing countries provides a useful analogy with which to evaluate trauma or health patterns of an ancient society. This paper presents a systematic analysis of cranial and postcranial skeletal trauma among 223 adults who were excavated by George Reisner in 1923 from the city of Kerma (1750,1550 BC), Egypt's ancient nemesis in the struggle for control of the Nile River trade route. A total of 156 injuries (fractures, dislocations and muscle pulls among the skull, long bones, extremities and torso) were observed among 88 individuals, 48 of whom had one injury only. The skull was the most frequently traumatized element (11.2%) followed by the ulna (8.3%); 2.4% (48/2029) long bones were fractured. The modal distribution of the Kerma fractures was compared to the fracture distributions of two samples from India and Nigeria where falls were the most common cause of injury. Some characteristics of the three injury patterns were shared: males suffered the greatest frequency of injury, the economically active people (25 to 50 years of age) presented the most injuries among adults, and a small proportion of the victims had more than one major injury. However, the Kerma distribution of the fractured bones varied dramatically from the clinical injury distributions: the ulna and skull were among the least frequently injured bones in the modern samples, while the radius, humerus and lower leg were the most commonly traumatized elements among the modern people, but rare among the ancients. The configuration of the ulna and skull injuries at Kerma was characteristic of those associated with blunt force trauma in other clinical assessments and the absence of these specific lesions from the modern samples where accident was the primary injury mechanism presents a persuasive argument for interpersonal violence among the ancient Kerma people. Copyright © 2004 John Wiley & Sons, Ltd. [source] Ancient injury recidivism: an example from the Kerma period of ancient NubiaINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 2 2002Margaret Judd Abstract A topical trend in clinical research has been the study of repeat trauma, referred to by clinicians as "injury recidivism," which lends itself to the assessment of accumulated injuries among ancient people. The present investigation examined the healed injuries among two archaeological skeletal samples from the Kerma period (ca. 2500,1500 BC) of Sudanese Nubia. Both groups were known to have a high prevalence of multiple trauma,80% of 54 adults from the rural sites (O16 and P37) located near Dongola and 42% of 212 adults from the urban site of Kerma sustained nonfatal injuries. It was observed that a higher frequency of multi-injured adults displayed one or more violence-associated injury (cranial trauma, parry fracture). When all injuries were considered 38% of individuals with violence-related injuries had other traumatic lesions in contrast to 22% of individuals who experienced injuries associated with accidental falls (e.g., Colles', Smiths', Galeazzi, and paired forearm fractures), although this difference was not significant. When only the skulls and long bones were evaluated 81% of adults with multiple injuries to these major bones bore one or more violence-related injuries, while 60% of adults with single injuries sustained violence-related injuries. Most individuals with multiple injuries were male and less than 35 years of age; there was no significant difference in the frequency of violence- or accident-related multiple injury between the rural and urban communities. Although it cannot be established whether or not some of an individual's injuries were experienced during simultaneous or independent incidents, the pattern of multiple injury among these two ancient Nubian skeletal samples reflected the profile of injury recidivism observed by modern clinicians cross-culturally. Copyright © 2002 John Wiley & Sons, Ltd. [source] Positive Regulation of Adult Bone Formation by Osteoblast-Specific Transcription Factor Osterix,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2009Wook-Young Baek Abstract Osterix (Osx) is essential for osteoblast differentiation and bone formation, because mice lacking Osx die within 1 h of birth with a complete absence of intramembranous and endochondral bone formation. Perinatal lethality caused by the disruption of the Osx gene prevents studies of the role of Osx in bones that are growing or already formed. Here, the function of Osx was examined in adult bones using the time- and site-specific Cre/loxP system. Osx was inactivated in all osteoblasts by Col1a1-Cre with the activity of Cre recombinase under the control of the 2.3-kb collagen promoter. Even though no bone defects were observed in newborn mice, Osx inactivation with 2.3-kb Col1a1-Cre exhibited osteopenia phenotypes in growing mice. BMD and bone-forming rate were decreased in lumbar vertebra, and the cortical bone of the long bones was thinner and more porous with reduced bone length. The trabecular bones were increased, but they were immature or premature. The expression of early marker genes for osteoblast differentiation such as Runx2, osteopontin, and alkaline phosphatase was markedly increased, but the late marker gene, osteocalcin, was decreased. However, no functional defects were found in osteoclasts. In summary, Osx inactivation in growing bones delayed osteoblast maturation, causing an accumulation of immature osteoblasts and reducing osteoblast function for bone formation, without apparent defects in bone resorption. These findings suggest a significant role of Osx in positively regulating osteoblast differentiation and bone formation in adult bone. [source] Cholesterol-Sensing Receptors, Liver × Receptor , and ,, Have Novel and Distinct Roles in Osteoclast Differentiation and ActivationJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2006Kirsten M Robertson Abstract The liver × receptor (,,,) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXR,,/,, LXR,,/,, and LXR,,/,,,/, mice show that both LXR, and , are also important for bone turnover, mainly by regulating osteoclast differentiation/activity. Introduction: The liver × receptors (,,,) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development. Materials and Methods: pQCT was performed on both male and female LXR,,/,, LXR,,/,, LXR,,/,,,/,, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers. Results: At the mRNA level, LXR, was more highly expressed than LXR, in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXR,,/, mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXR,,/, mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels. Conclusions: Our findings show that both LXRs influence cellular function within the bone, with LXR, having an impact on osteoclast activity, primarily in cortical bone, whereas LXR, modulates trabecular bone turnover. [source] Bone Morphogenetic Protein 2 Induces Cyclo-oxygenase 2 in Osteoblasts via a Cbfa1 Binding Site: Role in Effects of Bone Morphogenetic Protein 2 In Vitro and In VivoJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2005Daichi Chikazu Abstract We tested the hypothesis that induction of cyclo-oxygenase (COX) 2 mediates some effects of bone morphogenetic protein (BMP) 2 on bone. BMP-2 induced COX-2 mRNA and prostaglandin (PG) production in cultured osteoblasts. BMP-2 increased luciferase activity in calvarial osteoblasts from mice transgenic for a COX-2 promoter-luciferase reporter construct (Pluc) and in MC3T3-E1 cells transfected with Pluc. Deletion analysis identified the -300/-213-bp region of the COX-2 promoter as necessary for BMP-2 stimulation of luciferase activity. Mutation of core-binding factor activity 1 (muCbfa1) consensus sequence (5,-AACCACA-3,) at -267/-261 bp decreased BMP-2 stimulation of luciferase activity by 82%. Binding of nuclear proteins to an oligonucleotide spanning the Cbfa1 site was inhibited or supershifted by specific antibodies to Cbfa1. In cultured osteoblasts from calvariae of COX-2 knockout (-/-) and wild-type (+/+) mice, the absence of COX-2 expression reduced the BMP-2 stimulation of both ALP activity and osteocalcin mRNA expression. In cultured marrow cells flushed from long bones, BMP-2 induced osteoclast formation in cells from COX-2+/+ mice but not in cells from COX-2,/, mice. In vivo, BMP-2 (10 ,g/pellet) induced mineralization in pellets of lyophilized collagen implanted in the flanks of mice. Mineralization of pellets, measured by microcomputed tomography (,CT), was decreased by 78% in COX-2,/, mice compared with COX-2+/+ mice. We conclude that BMP-2 transcriptionally induces COX-2 in osteoblasts via a Cbfa1 binding site and that the BMP-2 induction of COX-2 can contribute to effects of BMP-2 on osteoblastic differentiation and osteoclast formation in vitro and to the BMP-2 stimulation of ectopic bone formation in vivo. [source] Oropharyngeal Skeletal Disease Accompanying High Bone Mass and Novel LRP5 Mutation,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2005Michael R Rickels Abstract Gain-of-function mutation in the gene encoding LRP5 causes high bone mass. A 59-year-old woman carrying a novel LRP5 missense mutation, Arg154Met, manifested skeletal disease affecting her oropharynx as well as dense bones, showing that exuberant LRP5 effects are not always benign. Introduction: Gain-of-function mutation (Gly171Val) of LDL receptor-related protein 5 (LRP5) was discovered in 2002 in two American kindreds with high bone mass and benign phenotypes. In 2003, however, skeletal disease was reported for individuals from the Americas and Europe carrying any of six novel LRP5 missense mutations affecting the same LRP5 protein domain. Furthermore, in 2004, we described a patient with neurologic complications from dense bones and extensive oropharyngeal exostoses caused by the Gly171Val defect. Materials and Methods: A 59-year-old woman was referred for dense bones. Three years before, mandibular buccal and lingual exostoses (osseous "tori") were removed because of infections from food trapping between the teeth and exostoses. Maxillary buccal and palatal exostoses were asymptomatic. Radiographic skeletal survey showed marked thickening of the skull base and diaphyses of long bones (endosteal hyperostosis). BMD Z scores assessed by DXA were +8.5 and +8.7 in the total hip and L1 -L4 spine (both ,195% average control), respectively. LRP5 mutation analysis was carried out for the LRP5 domain known to cause high bone mass. Results: Biochemical evaluation excluded most secondary causes of dense bones, and male-to-male transmission in her family indicated autosomal dominant inheritance. PCR amplification and sequencing of LRP5 exons 2-4 and adjacent splice sites revealed heterozygosity for a new LRP5 missense mutation, Arg154Met. Conclusions: LRP5 Arg154Met is a novel defect that changes the same first ",-propeller" module as the eight previously reported LRP5 gain-of-function missense mutations. Arg154Met alters a region important for LRP5 antagonism by dickkopf (Dkk). Therefore, our patient's extensive oropharyngeal exostoses and endosteal hyperostosis likely reflect increased Wnt signaling and show that exuberant LRP5 effects are not always benign. [source] Possible Roles of Runx1 and Sox9 in Incipient Intramembranous Ossification,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2004Takashi Yamashiro DDS Abstract We evaluated the detailed expression patterns of Runx1 and Sox9 in various types of bone formation, and determined whether Runx1 expression was affected by Runx2 deficiency and Runx2 expression by Runx1 deficiency. Our results indicate that both Runx1 and Sox9 are intensely expressed in the future osteogenic cell compartment and in cartilage. The pattern of Runx1 and Sox9 expression suggests that both genes could potentially be involved in incipient intramembranous bone formation during craniofacial development. Introduction:Runx1, a gene essential for hematopoiesis, contains RUNX binding sites in its promoter region, suggesting possible cross-regulation with Runx2 and potential regulatory roles in bone development. On the other hand, Sox9 is essential for chondrogenesis, and haploinsufficiency of Sox9 leads to premature ossification of the skeletal system. In this study, we studied the possible roles of Runx1 and Sox9 in bone development. Materials and Methods:Runx1, Runx2/Osf2, and Sox9 expression was evaluated by in situ hybridization in the growing craniofacial bones of embryonic day (E)12,16 mice and in the endochondral bone-forming regions of embryonic and postnatal long bones. In addition, we evaluated Runx2/Osf2 expression in the growing face of Runx1 knockout mice at E12.5 and Runx1 expression in Runx2 knockout mice at E14.5. Results:Runx1 and Sox9 were expressed in cartilage, and the regions of expression expanded to the neighboring Runx2 -expressing osteogenic regions. Expression of both Runx1 and Sox9 was markedly downregulated on ossification. Runx1 and Sox9 expression was absent in the regions of endochondral bone formation and in actively modeling or remodeling bone tissues in the long bones as well as in ossified craniofacial bones. Runx2 expression was not affected by gene disruption of Runx1, whereas the expression domains of Runx1 were extended in Runx2,/, mice compared with wildtype mice. Conclusions:Runx1 and Sox9 are specifically expressed in the osteogenic cell compartments in the craniofacial bones and the bone collar of long bones, and this expression is downregulated on terminal differentiation of osteoblasts. Our results suggest that Runx1 may play a role in incipient intramembranous bone formation. [source] Targeted Expression of SHH Affects Chondrocyte Differentiation, Growth Plate Organization, and Sox9 Expression,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2004Sara Tavella Abstract The role of Hedgehogs (Hh) in murine skeletal development was studied by overexpressing human Sonic Hedgehog (SHH) in chondrocytes of transgenic mice using the collagen II promoter/enhancer. Overexpression caused a lethal craniorachischisis with major alterations in long bones because of defects in chondrocyte differentiation. Introduction: Hedgehogs (Hhs) are a family of secreted polypeptides that play important roles in vertebrate development, controlling many critical steps of cell differentiation and patterning. Skeletal development is affected in many different ways by Hhs. Genetic defects and anomalies of Hhs signaling pathways cause severe abnormalities in the appendicular, axial, and cranial skeleton in man and other vertebrates. Materials and Methods: Genetic manipulation of mouse embryos was used to study in vivo the function of SHH in skeletal development. By DNA microinjection into pronuclei of fertilized oocytes, we have generated transgenic mice that express SHH specifically in chondrocytes using the cartilage-specific collagen II promoter/enhancer. Transgenic skeletal development was studied at different embryonic stages by histology. The expression pattern of specific chondrocyte molecules was studied by immunohistochemistry and in situ hybridization. Results: Transgenic mice died at birth with severe craniorachischisis and other skeletal defects in ribs, sternum, and long bones. Detailed analysis of long bones showed that chondrocyte differentiation was blocked at prehypertrophic stages, hindering endochondral ossification and trabecular bone formation, with specific defects in different limb segments. The growth plate was highly disorganized in the tibia and was completely absent in the femur and humerus, leading to skeletal elements entirely made of cartilage surrounded by a thin layer of bone. In this cartilage, chondrocytes maintained a columnar organization that was perpendicular to the bone longitudinal axis and directed toward its outer surface. The expression of SHH receptor, Patched-1 (Ptc1), was greatly increased in all cartilage, as well as the expression of parathyroid hormone-related protein (PTHrP) at the articular surface; while the expression of Indian Hedgehog (Ihh), another member of Hh family that controls the rate of chondrocyte maturation, was greatly reduced and restricted to the displaced chondrocyte columns. Transgenic mice also revealed the ability of SHH to upregulate the expression of Sox9, a major transcription factor implicated in chondrocyte-specific gene expression, in vivo and in vitro, acting through the proximal 6.8-kb-long Sox9 promoter. Conclusion: Transgenic mice show that continuous expression of SHH in chondrocytes interferes with cell differentiation and growth plate organization and induces high levels and diffuse expression of Sox9 in cartilaginous bones. [source] An In Vitro Study of the Ultrasonic Axial Transmission Technique at the Radius: 1-MHz Velocity Measurements Are Sensitive to Both Mineralization and Intracortical Porosity,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2004Emmanuel Bossy Abstract The ultrasonic axial transmission technique allows for investigating skeletal sites such as the cortical layer of long bones (radius, tibia, phalanges). Using synchrotron radiation ,CT, we investigated, in vitro, the relationships between 1-MHz axial transmission SOS measurements at the radius and site-matched measurements of C.Th, POR, MIN, and vBMD. Introduction: The ultrasonic axial transmission technique allows for investigating skeletal sites such as the cortical layer of long bones (radius, tibia, phalanges). Materials and Methods:Using synchrotron radiation ,CT, we investigated, in vitro, the relationships between 1-MHz axial transmission speed of sound (SOS) measurements at the radius and site-matched measurements of cortical thickness (C.Th), intracortical porosity (POR), tissue mineralization (MIN), and volumetric BMD (vBMD). SOS measurements were based on bidirectional axial transmission and were performed with a 1-MHz proprietary probe on 39 excised human radii. Results: The highest correlations between SOS values and bone parameters (R2SOS/POR = 0.28, p < 10,3; R2SOS/MIN = 0.38, p < 10,4; R2SOS/vBMD = 0.57, p < 10,3) were found for bone parameters assessed in a 1-mm-thick periosteal region of the cortex rather than throughout the whole cortex. The observed moderate correlation between SOS and C.Th values (R2SOS/C.Th = 0.20, p < 10,2) disappeared when controlled for other variables. The two best multilinear predictive models, including either BMD alone or the pair of dependent variables MIN and POR (all assessed in the periosteal cortex), were equally accurate in predicting SOS values (R2SOS/(POR,MIN) = 0.59, p < 10,5; R2SOS/vBMD = 0.57, p < 10,5). Conclusion: For the first time, the respective adjusted contributions of POR (,24 m/s%,1) and tissue mineralization (+3.5 m/s/mg/cm,3) to SOS values were assessed. These results suggest potential sensitivity of axial transmission SOS values to changes in cortical bone status under different pathological conditions or treatments affecting POR and/or tissue mineralization. [source] Effects of Liver-Derived Insulin-Like Growth Factor I on Bone Metabolism in Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2002Klara Sjögren Abstract Insulin-like growth factor (IGF) I is an important regulator of both skeletal growth and adult bone metabolism. To better understand the relative importance of systemic IGF-I versus locally expressed IGF-I we have developed a transgenic mouse model with inducible specific IGF-I gene inactivation in the liver (LI-IGF-I,/,). These mice are growing normally up to 12 weeks of age but have a disturbed carbohydrate and lipid metabolism. In this study, the long-term effects of liver-specific IGF-I inactivation on skeletal growth and adult bone metabolism were investigated. The adult (week 8,55) axial skeletal growth was decreased by 24% in the LI-IGF-I,/, mice whereas no major reduction of the adult appendicular skeletal growth was seen. The cortical cross-sectional bone area, as measured in the middiaphyseal region of the long bones, was decreased in old LI-IGF-I,/, mice. This reduction in the amount of cortical bone was caused mainly by decreased periosteal circumference and was associated with a weaker bone determined by a decrease in ultimate load. In contrast, the amount of trabecular bone was not decreased in the LI-IGF-I,/, mice. DNA microarray analysis of 30-week-old LI-IGF-I,/, and control mice indicated that only four genes were regulated in bone whereas ,40 genes were regulated in the liver, supporting the hypothesis that liver-derived IGF-I is of minor importance for adult bone metabolism. In summary, liver-derived IGF-I exerts a small but significant effect on cortical periosteal bone growth and on adult axial skeletal growth while it is not required for the maintenance of the trabecular bone in adult mice. [source] | |||||||||||||||||||