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The fluoroaluminate (AlF 4- ) ion and sodium fluoride (NaF) have previously been shown to be bone cell mitogens. This study sought to determine whether the bone cell mitogenic action of AlF 4- and/or NaF would involve the insulin-like growth factor (IGF) regulatory system. We evaluated the effect of mitogenic doses of AlF 4- and NaF on the mRNA levels and the...
Physical activity during the first three decades of life may increase peak bone mass and reduce future osteoporosis risk. The aim of this study was to determine the extent to which different components of physical activity may influence bone mineral status within a representative population sample of young men and women. Bone mineral density (BMD) and content (BMC) were determined at the lumbar spine...
Inhibition of the cyteine proteinase, cathepsin K (E.C. 3.4.22.38) has been postulated as a means to control osteoclast-mediated bone resorption. The preferred animal models for evaluation of antiresorptive activity are in the rat. However, the development of compounds that inhibit rat cathepsin K has proven difficult because the human and rat enzymes differ in key residues in the active site. In...
Parathyroid hormone (PTH) is a promising anabolic agent for the treatment of osteoporosis. However, PTH is also potently catabolic. To help delineate the molecular mediators of PTH's opposing effects on skeletal metabolism, we have examined PTH-induced regulator of G-protein signaling-2 (RGS-2) expression and function in murine osteoblasts. RGS proteins are GTPase-activating proteins (GAPs) that regulate...
Platelets are activated at fracture sites or upon the insertion of implants as a consequence of vascular disruption and secrete the contents of their granules into the developing hematoma. The regeneration of injured tissue requires bone remodeling and the resorbing activity of osteoclasts. To test our hypothesis that platelets can stimulate osteoclastogenesis, we examined the effects of supernatants...
Human cementifying fibroma (HCF) is a benign fibro-osseous neoplasm of periodontal ligament (PDL) origin containing varying amounts of mineralized material resembling cementum. In the present study, we established cell lines from HCF, which were detected in the mandible of a 54-year-old Japanese man. To obtain immortalized cell clones, we undertook transfection with temperature-sensitive simian virus-40...
The role of α-smooth muscle actin (SMA)-expressing fibroblasts in the contraction of skin wounds has been known for three decades. Recent studies have demonstrated that osteoblasts can also express the gene for this contractile muscle actin isoform and can contract a collagen-glycosaminoglycan analog of extracellular matrix in vitro. These findings provided rationale for the hypothesis that SMA-expressing...
We report the establishment in vitro of three-dimensional (3D) cultures of human osteoblasts (hOB) derived from normal adults and supported uniquely by the extracellular matrix (ECM) they deposit. Osteoblasts were cultured in 3D cultures in vitro for up to 120 days. The 3D cultures, examined at 25, 31, and 48 days, expressed protein markers of osteoblastic cells, namely osteonectin, collagen type...
Subclinical vitamin D deficiency may be common in certain subgroups in the U.S., but to date vitamin D data from other groups in the population have not been available. We used serum 25-hydroxyvitamin D (25-OHD) data from 18,875 individuals examined in the Third National Health and Nutrition Examination Survey (NHANES III 1988-1994) to assess the vitamin D status of selected groups of the noninstitutionalized...
The bicondylar angle is the angle between the diaphysis of the femur and a line perpendicular to the infracondylar plane. The presence of a femoral bicondylar angle in Australopithecus afarensis indicates that these 3.5-million-year-old hominids were bipedal. Many studies have linked the formation of the femoral bicondylar angle with bipedality, but the mechanism for the formation of the angle is...
The aim of this study was to model the effect of short (3 year) treatments for osteoporosis at different times after menopause on the risk of osteoporotic fracture and to assess the impact of strategies to target high-risk individuals. Treatment efficacy for hip, proximal forearm, shoulder, and spine fracture were computed from the relationship between bone mineral density (BMD) and fracture in women...
Bone marrow stroma contain pluripotential cells with the potential to differentiate into various mesenchymal cell lineages. We compared the effect of cortisol and bone morphogenetic protein-2 (BMP-2) on the differentiation of murine ST-2 stromal cells into mature osteoblasts or adipocytes. ST-2 cells were cultured for 3-27 days in the presence of 10% fetal bovine serum, 100 μg/mL ascorbic acid, and...
The signals that allow bone to adapt to its mechanical environment most likely involve strain-mediated fluid flow through the canalicular channels. Fluid can only be moved through bone by cyclic loading, and the shear stresses generated on bone cells are proportional to the rate of loading. The proportional relation between fluid shear stresses on cells and loading rate predicts that the magnitude...
Parathyroid hormone-related peptide (PTHrP) is a mediator of local osteolysis due to breast cancer. Three isoforms of PTHrP, (1-139), (1-141), and (1-173), are products of alternative splicing in humans, but the specific contribution of each of these isoforms to osteolytic metastasis caused by breast cancer has not been evaluated. To determine the role of PTHrP isoforms in breast cancer metastasis...
Most of the questionnaires available to estimate the daily physical activity levels of humans are based on measuring the intensity of these activities as multiples of resting metabolic rate (METs). Metabolic intensity of physical activities is the most important component for evaluating effects on cardiopulmonary fitness. However, animal studies have indicated that for effects on bone mass the intensity...
We have previously shown that there are pronounced age-related changes in human vertebral cancellous bone density and microarchitecture. However, the magnitude of these changes seemed to be dependent on zone location in the vertebral body-the central third vs. the areas adjacent to the endplates. The aim of the present study was, therefore, to investigate whether such zone-specific differences could...
Calcitonin was discovered as a hypocalcemic principal that was initially thought to originate from the parathyroid gland. This view was corrected subsequently, and an origin from the thyroid C cells was documented. The purification and sequencing of various calcitonins soon followed. Calcitonin is a 32-amino-acid-long peptide with an N-terminal disulfide bridge and a C-terminal prolineamide residue...
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