Bone Physiology (bone + physiology)

Distribution by Scientific Domains


Selected Abstracts


Vitamin D and Bone Physiology: Demonstration of Vitamin D Deficiency in an Implant Osseointegration Rat Model

JOURNAL OF PROSTHODONTICS, Issue 6 2009
James Kelly DDS
Abstract Purpose: The patient population varies in nutritional deficiencies, which may confound the host response to biomaterials. The objective of this study was to evaluate the effect of a common deficiency of vitamin D on implant osseointegration in the rat model. Materials and Methods: Male Sprague-Dawley rats were maintained under the cessation of vitamin D intake and UV exposure. The serum levels of 1,25(OH)2D3, 25 OHD3, Ca, and P were determined. Miniature cylindrical Ti6Al4V implants (2-mm long, 1-mm diameter) were fabricated with double acid-etched (DAE) surface or modified DAE with discrete crystalline deposition (DCD) of hydroxyapatite nanoparticles. DAE and DCD implants were placed in the femurs of vitamin D-insufficient and control rats. After 14 days of healing, the femur-implant samples were subjected to implant push-in test and nondecalcified histology. The surfaces of recovered implant specimens after the push-in test were further evaluated by scanning electron microscopy (SEM). Results: The decreased serum level of 25 OHD3 demonstrated the establishment of vitamin D insufficiency in this model. The implant push-in test revealed that DAE and DCD implants in the vitamin D-insufficient group (15.94 8.20 N, n = 7; 15.63 3.96 N, n = 7, respectively) were significantly lower than those of the control group (24.99 7.92 N, n = 7, p < 0.05; 37.48 17.58 N, n = 7, p < 0.01, respectively). The transcortical bone-to-implant contact ratio (BIC) was also significantly decreased in the vitamin D-insufficient group. SEM analyses further suggested that the calcified tissues remaining next to the implant surface after push-in test appeared unusually fragmented. Conclusions: The effect of vitamin D insufficiency significantly impairing the establishment of Ti6Al4V implant osseointegration in vivo was unexpectedly profound. The outcome of Ti-based endosseous implants may be confounded by the increasing prevalence of vitamin D insufficiency in our patient population. [source]


The function of the Egr1 transcription factor in cartilage formation and adaptation to microgravity in zebrafish, Danio rerio

JOURNAL OF APPLIED ICHTHYOLOGY, Issue 2 2010
M. Muller
Summary Osteoporosis is one of the major concerns for an ageing human population and for passengers on long-term space flights. Teleosts represent a potentially interesting alternative for studying bone physiology. In zebrafish (Danio rerio), the cartilaginous elements that form the pharyngeal arches derive from cranial neural crest cells, whose proper patterning and morphogenesis require reciprocal interactions with other tissue types such as pharyngeal endoderm, ectoderm and mesoderm. We show how the zebrafish can be used to study the function of signal transduction pathways, such as the Fgf pathway, or that of particular genes, such as the zinc finger transcription factor Egr1, in pharyngeal skeleton formation and maintenance. We investigate the changes caused by microgravity and chemical treatments on zebrafish. We analyze early gene expression modification using whole genome microarray experiments and the long-term consequences by staining bone structures. [source]


Overexpression of Lysyl Hydroxylase-2b Leads to Defective Collagen Fibrillogenesis and Matrix Mineralization,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2005
Suchaya Pornprasertsuk
Abstract Several MC3T3-E1 cell-derived clones expressing higher levels of LH2b were analyzed for their abilities to form collagen fibrils and mineralization. The clones all exhibited smaller collagen fibrils and defective matrix mineralization in vitro and in vivo, indicating a critical role of LH2b-catalyzed post-translational modifications of collagen in bone matrix formation and mineralization. Introduction: We have recently shown that lysyl hydroxylase (LH) 2b, through its action on the telopeptidyl lysine residues of collagen, regulates collagen cross-linking pathway in the osteoblastic cell line, MC3T3-E1. To further elucidate the roles of LH2b in bone physiology, the effects of overexpression of LH2b on collagen fibrillogenesis and matrix mineralization were investigated. Materials and Methods: Several MC3T3-E1-derived osteoblastic cell clones expressing higher levels of LH2b (S clones) and two controls (i.e., MC3T3-E1 cells and those transfected with an empty vector) were cultured. MALDI-TOF mass spectrometry was used to identify the LH2b. The collagen fibrillogenesis in the cultures was characterized by transmission electron microscopy, and the ability of these clones and cells to form mineralized matrix was analyzed by both in vitro and in vivo mineralization assays. Results: The diameter of collagen fibrils in the S clone cultures was markedly smaller than that of the controls. The onset of matrix mineralization in the S clones was significantly delayed, and considerably fewer mineralized nodules were formed in their cultures in comparison with the controls. When transplanted into immunodeficient mice, the S clones failed to form mineralized matrices in vivo, whereas a bone-like mineralized matrix was well formed by the controls. The diameter of the collagen fibrils and the timing/extent of matrix mineralization in vitro were inversely correlated with the level of LH2b. In vitro cell differentiation was unaffected by the LH2b overexpression. Conclusions: These results indicate a critical role of LH2b catalyzed post-translational modification of collagen (i.e., telopeptidyl lysine hydroxylation and subsequent cross-linking) in collagen matrix formation and mineralization in bone. [source]


Effect of lacunocanalicular architecture on hydraulic conductance in bone tissue: Implications for bone health and evolution

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 2 2003
Sanjay Mishra
Abstract Bone tissue health depends largely on efficient fluid and solute transport between the blood supply and cells that are the living component of the tissue. We hypothesized that the lacunocanalicular hydraulic network, which is defined by the pericellular fluid space that is common to all bone tissue, is optimized to transport fluid and solutes between the blood supply and bone cells. An analytical study was carried out to evaluate the effect of osteonal architecture, including the osteon diameter, number of annular lamellar regions, and number and length of canalicular channels, on fluid transport between the blood supply and bone cells. On the basis of this analysis, we conclude that osteon size is limited to the distance over which fluid and solutes can be transported efficiently between the blood supply and cells. This analytic model suggests that hydraulic conductivity is highest in lamellar regions closest to the Haversian canal (HC) and decreases with increasing distance from the blood supply, reaching a plateau after the fifth lamella (169 ,m radius). Furthermore, an increase in the diameter of the HC, or a decrease in the length of canaliculi, reduces the hydraulic conductivity within the lacunocanalicular network. Applying the principle of minimal expenditure of energy to this analysis, the path distance comprising five or six lamellar regions represents an effective limit for fluid and solute transport between the blood supply and cells; beyond this threshold, hydraulic resistance in the network increases and additional energy expenditure is necessary for further transportation. This suggests that transport is optimized to meet metabolic demands concomitant with a minimal expenditure of energy. This fundamental new insight into bone structure and physiology may provide a new basis of understanding for tissue engineering, bone physiology in health and disease, and evolutionary biology. Anat Rec Part A 273A:752,762, 2003. 2003 Wiley-Liss, Inc. [source]


Teriparatide (Biosynthetic Human Parathyroid Hormone 1,34): A New Paradigm in the Treatment of Osteoporosis

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2004
Kim T. Brixen
Biosynthetic human parathyroid hormone 1,34 (teriparatide) was recently approved in the EU and the USA as the first anabolic treatment of osteoporosis. The effects of teriparatide are mediated by the G-protein-dependent, parathyroid hormone receptor-1 in the cell membrane. The binding of the ligand to the receptor activates adenylate cyclase and a number of phospholipases (A, C, and D) and increases intracellular levels of cAMP and calcium. Intermittent teriparatide increases the number of osteoblasts and bone formation by activation of pre-existing osteoblasts, increased differentiation of lining cells, and reduced osteoblast apoptosis. Anabolic effects of teriparatide on bone have been demonstrated in several species. It increases bone mass, structural integrity, bone diameter, and bone strength. Clinical efficacy was demonstrated in a randomized study comprising 1637 post-menopausal women with osteoporosis showing a 65% and 35% reduction of the relative risk of vertebral and appendicular fractures, respectively, during 18 months of treatment. Moreover, bone mineral density in the lumbar spine and hip increased by 9.7% and 2.6%, respectively. Similar effects on bone mineral density have been reported in men with osteoporosis and in glucocorticoid-induced osteoporosis, however, fracture data are limited in these groups. Direct comparison with alendronate revealed that teriparatide has a more pronounced effect on bone mineral density. Teriparatide should be used in combination with calcium plus vitamin D, and may be combined with hormonal replacement therapy. In contrast, alendronate attenuates the effect of teriparatide. The efficacy of other combinations remains uncertain. After termination of teriparatide, bone mineral density of the lumbar spine is reduced by approximately 2,3% after 2 1/2 years. This decrease is prevented by treatment with bisphosphonates. The most frequent adverse effects with teriparatide are nausea, headache, dizziness, and leg cramps, however, only the latter two differed significantly between the groups receiving teriparatide 20 ,g/day and placebo. In the pivotal clinical study, reduced dosage or termination of therapy due to hypercalcaemia was necessary in 3% and 0.2%, respectively. In a rat toxicology study, in which teriparatide was administered in high dosages for an extended period of time, osteosarcoma was seen in a significant number of animals. However, none of the approximately 2800 patients in clinical trials has developed osteosarcoma. Teriparatide constitutes a break-through in the treatment of severe osteoporosis, although a number of issues about the optimal use of teriparatide remains unsettled. The published data provide proof of concept on anabolic therapy which changes several paradigms of bone physiology. Other parathyroid hormone analogues are being investigated in clinical trials and the development of non-peptide, small molecules targeted at the parathyroid hormone receptor may be envisaged. [source]