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Recent data have shown that activation of Gi-protein-coupled receptors in osteoblast-like cells enhances the proliferation and differentiation of these cells. In the present study, we investigated the effect of epinephrine, an agonist of Gi-protein-coupled receptors in MC3T3-E1 cells, on Pi transport, type III Pi transporter expression, and the signaling mechanism(s) involved in this response. Epinephrine...
In mature trabecular bone, both density and trabecular orientation are adapted to external mechanical loads. Few quantitative data are available on the development of architecture and mechanical adaptation in juvenile trabecular bone. We studied the hypothesis that a time lag occurs between the adaptation of trabecular density and the adaptation of trabecular architecture during development. To investigate...
Long-term in vivo studies have highlighted smoking as a risk factor in postmenopausal osteoporosis, bone fracture incidence, and increased nonunion rates. In contrast, there are few data postulating the effects of smoking at the cellular level in human skeletal tissue. In this study, we present novel evidence demonstrating that the nicotinic receptor α4 subunit is present in human primary bone cells...
To test the hypothesis that the effect of trabecular microarchitecture on bone strength varies with the duration of estrogen loss, we evaluated the relationship between three-dimensional (3D) parameters for trabecular microarchitecture and bone minerals with the compressive load of the lumbar vertebra in rats. Female Sprague-Dawley rats (n = 190) were divided into 19 groups. Ten rats were killed at...
Demineralization and muscle atrophy, common among patients with hemiplegia, may be risk factors for future hip fracture. The aim of this longitudinal study was to investigate changes in lean (muscle) mass and bone mineral content (BMC) of the legs during the first year after stroke according to the patient's ambulatory level. Twenty-five patients immobilized due to acute stroke were followed. BMC...
Osteoclasts are generated from peripheral blood mononuclear cells (PBMNCs) in the presence of soluble receptor activator of NFκB ligand (sRANKL) and macrophage colony-stimulating factor (M-CSF). We show that human osteoclast formation is enhanced when PBMNCs are cultured in the presence of transforming growth factor (TGF)-β and M-CSF prior to the addition of sRANKL. The effect was only observed in...
Cyclosporine A (CsA), a potent immunosuppressant used in transplantation, induces increased formation with excess resorption in the rat with resultant osteopenia. These findings are confirmed in the human model. Transforming growth factor-β (TGF-β) is reported to be involved in the coupling of bone formation with resorption and in vivo and in vitro stimulates osteoblasts, and in vitro inhibits osteoclasts...
We examined the effects of a third generation bisphosphonate [YM-175; disodium dihydrogen (cycloheptylamino)-methylene-1,1-bisphosphonate] on osteoclasts in osteosclerotic (oc/oc) mice to elucidate the cellular mechanism for incorporation of the bisphosphonate. Osteoclasts of oc/oc mice were in direct contact with bone matrix but devoid of ruffled borders. Tartrate-resistant acid phosphatase (TRAPase)...
Sulfate conjugation is an important pathway in the metabolism of many drugs, xenobiotic compounds, and hormones. Sulfotransferases (SULTs) catalyze these reactions and have been detected and characterized in various human tissues including the liver and small intestine. Substrates for SULTs that include estrogen and thyroid hormones have well-established roles affecting skeletal integrity and disease...
We succeeded in developing a novel rabbit model of nonsteroid and nontraumatic osteonecrosis (ON) by use of a single- and low-dose lipopolysaccharide (LPS) injection. This model is simple and highly reproducible for the frequent development of multifocal and widespread ON lesions. Male adult Japanese white rabbits intravenously injected with a single injection of 10 μg/kg body weight of LPS were histopathologically...
We investigated the effects of ovariectomy (ovx) and estrogen replacement therapy (ERT) on bone mineral density (BMD) and arthritis severity in rats with collagen-induced arthritis (CIA). Seven-month-old female Sprague-Dawley rats were separated into a sham group (n = 8), CIA group (n = 14), ovx group (n = 10), CIA + ovx group (n = 11), and CIA + ovx + ERT group (n = 14). In these groups, ovx was...
Previous studies have demonstrated that, in osteoblast-like MC3T3-E1 cells, various endothelin peptides and their homologous sarafotoxins generate prostaglandin E 2 (PGE 2 ) release through an ET A receptor subtype. In this study, biphasic Ca 2+ signals elicited with endothelin (ET)-1, ET-2, ET-3, β-ET, S6a1, and S6b (ET/S6) were measured by microspectrofluorimetric...
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