Osteoclasts are a major component of bone metabolism in physiologic condition and in rheumatoid arthritis (RA). RA is a chronic, autoimmune, inflammatory disease primarily affecting the joints. Joint inflammation leads to cartilage and bone destruction by osteoclast activation. This osteoclast activation leads to typical RA symptoms and is the therapeutic target. Several kinds of drugs are used...

GPR55 is a G protein-coupled receptor recently shown to be activated by certain cannabinoids and by lysophosphatidylinositol (LPI). However, the physiological role of GPR55 remains unknown. Given the recent finding that the cannabinoid receptors CB(1) and CB(2) affect bone metabolism, we examined the role of GPR55 in bone biology. GPR55 was expressed in human and mouse osteoclasts and osteoblas...

Estrogen deficiency in menopause is a major cause of osteoporosis in women. Estrogen acts to maintain the appropriate ratio between bone-forming osteoblasts and bone-resorbing osteoclasts in part through the induction of osteoclast apoptosis. Recent studies have suggested a role for Fas ligand (FasL) in estrogen-induced osteoclast apoptosis by an autocrine mechanism involving osteoclasts alone....

The origin of osteoclasts from mononuclear phagocytes and the addition of new nuclei to already differentiated osteoclasts have already been documented by several authors, but the factors controlling these events have not yet been elucidated. With the aim of investigating this problem, monocytes, isolated from circulating blood of laying hens and cultured previously for 5 days, were added to os...

Blood monocytes are precursors of dendritic cells, macrophages, and osteoclasts. They are a heterogeneous cell population with differences in size, phenotype, and function. Although monocytes maintain several tissue-specific populations of immune cells in homeostasis, their contribution to populations of dendritic cells, macrophages, and osteoclasts is significantly increased in inflammation. I...

Calcitonin receptors have been characterized for the first time in isolated osteoclasts. These receptors have been demonstrated by autoradiographic and biochemical methods, and the cells have also been shown to respond to calcitonin with a dose-dependent increase in cyclic AMP. The receptors in rat osteoclasts are specific and of high affinity (dissociation constant, Kd, 1 to 6 X 10-10 M), and ...

The protein tyrosine kinase Pyk2 is highly expressed in osteoclasts, where it is primarily localized in podosomes. Deletion of Pyk2 in mice leads to mild osteopetrosis due to impairment in osteoclast function. Pyk2-null osteoclasts were unable to transform podosome clusters into a podosome belt at the cell periphery; instead of a sealing zone only small actin rings were formed, resulting in imp...

During the last two decades, ample evidence has been obtained that osteoclasts, the multinucleated calcified-matrix resorbing giant cells of bone, which form by fusion of mononuclear precursor cells, are of hematogenous origin. The evidence stems from experiments done in parabionts of labeled animals (1), studies on osteopetrotic animals and humans (2-4), and quail-chick and mouse-quail transpl...

This study sought to test whether targeted overexpression of osteoactivin (OA) in cells of osteoclastic lineage, using the tartrate-resistant acid phosphase (TRAP) exon 1B/C promoter to drive OA expression, would increase bone resorption and bone loss in vivo. OA transgenic osteoclasts showed ∼2-fold increases in OA mRNA and proteins compared wild-type (WT) osteoclasts. However, the OA expressi...

Genistein, a major phytoestrogen of soy, is considered a potential drug for prevention and treatment of postmenopausal osteoporosis. It is not clear whether mechanism of action of genistein on bone turnover is distinct from that of estradiol or raloxifene. The aim of the present study was to investigate the effects of genistein on the formation of osteoclasts from neonatal rat bone marrow cells...