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Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric...
Myostatin is a member of the bone morphogenetic protein/transforming growth factor-β (BMP/TGFβ) super-family of secreted differentiation factors. Myostatin is a negative regulator of muscle mass as shown by increased muscle mass in myostatin deficient mice. Interestingly, these mice also exhibit increased bone mass suggesting that myostatin may also play a role in regulating bone mass. To investigate...
To test the hypothesis that periosteal circumference (PC), which is associated with bone size through cross-sectional moment of inertia (CMI), has heritable components, we performed a linkage analysis using 633 MRL/SJL F 2 mice that have 14% difference in mean PC. PC was determined in femurs by use of peripheral quantitative computerized tomography (pQCT). The genome-wide scan identified nine...
The hypothesis of this study is that the mechanical integrity of the collagen network in bone deteriorates with age, and such adverse changes correlate with the decreased toughness of aged bone. To test the hypothesis, 30 human cadaveric femurs from donors ranging from 19 to 89 years of age were tested to determine the age-related changes in the mechanical properties of demineralized bone and fresh...
Recent studies have shown that stimulation of osteoclastogenesis in cocultures of osteoblasts and spleen cells in response to prostaglandin E 2 (PGE 2 ) is markedly decreased when the osteoblasts are derived from cells lacking either the EP 2 or the EP 4 receptor. Induction of osteoclast formation requires upregulation of receptor activator of nuclear factor-κB ligand...
Prostaglandin estradiol (PGE2) stimulates bone resorption by a cyclic AMP (cAMP)-dependent mechanism that involves prostaglandin E receptors of the EP2 and EP4 subtypes. We tested a potent selective EP4 antagonist (EP4RA), which blocks PGE2 binding to EP4 receptors. We examined the effects of EP4RA on osteoclastogenesis in murine marrow cultures, on cAMP production in primary osteoblastic (POb) cell...
Inbred strains of mice are increasingly being used as an animal model to investigate skeletal disorders relevant to humans. In the bone field, one of the most convenient endpoints for evaluating genetic, physiological, or pharmaceutical perturbations is the use of biochemical markers. To apply biochemical markers in an effective manner, it is of key importance to establish the biological variation...
Genetic variation in bone-regenerative capacity has not been studied in any animal model system. We developed a ''drill-hole'' model in the tail vertebra of inbred strains of mice that allows us to reproducibly introduce an injury with a defined boundary and quantify the rate of bone healing using the combination of high-resolution Faxitron X-ray imaging and the ChemiImager 4000 Low Light Imaging...
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