Colony-stimulating factor-1 (CSF-1) stimulates motility and cytoplasmic spreading in mature osteoclasts. Therefore, we examined the cellular events and intracellular signaling pathways that accompany CSF-1-induced spreading in normal osteoclasts. To explore the role c-src plays in these processes, we also studied osteoclasts prepared from animals with targeted disruption of the src gene. In nor...

The ultrastructure of osteoclasts was examined in fetal rat bones after stimulation or inhibition of resorption in culture. A central ruffled border area completely encircled by a clear zone was considered to represent the resorbing system of the cell. The proportion of ruffled border and clear zone in osteoclast cross sections was compared with changes in bone resorption as measured by the rel...

Heilongjiang, China SUMMARY: Receptor activator of nuclear factor kappa-B ligand (RANKL) acting on osteoblasts is an essential cytokine for osteoclast formation. Recent studies have shown that fluoride (F) can stimulate RANKL expression of osteoblasts. However, the effect of F under various levels of RANKL on osteoclast formation is not clear. In this study, stem cell technology was used to obs...

The use of proton pump inhibitors (PPIs) seems to be related to increased fracture risk but the mechanism is unclear. In an effort to clarify the mechanism, we evaluated the effect of omeprazole, a representative of the PPIs, on the expression of transcription factors in osteoclasts and osteoblasts. Murine RAW264.7 and MC3T3-E1 cells were used for osteoclast and osteoblast analysis, to which va...

Although both an active form of the vitamin D metabolite, 1,25(OH)2D3, and the vitamin D analogue, ED71 have been used to treat osteoporosis, anti-bone resorbing activity is reportedly seen only in ED71- but not in 1,25(OH)2D3 -treated patients. In addition, how ED71 inhibits osteoclast activity in patients has not been fully characterized. Recently, HIF1α expression in osteoclasts was demonstr...

The modeling and remodeling of bone requires activation and polarization of osteoclasts, achieved by reorganization of the cytoskeleton. Members of the Rho subfamily of small GTPases, including Cdc42, are known regulators of cytoskeletal components, but the role of these proteins in bone physiology and pathophysiology remains unclear. Here, we examined loss-of-function mice in which Cdc42 was s...

Bone resorption requires cooperation between osteoclasts and mononuclear accessory cells by mechanisms which have not been elucidated. Since multinucleated cells in giant cell tumors of bone have many phenotypic and functional characteristics of normal osteoclasts, we have examined the interaction between the bone-resorbing multinucleated cells and the distinct mononuclear stromal cells from th...

While platelet-activating factor (PAF) is produced in various diseases associated with bone resorption, its functions in bone metabolism remain unknown. Using PAF receptor-deficient mice, we evaluated the role of PAF in the development of bone resorption following ovariectomy, a model of postmenopausal osteoporosis. Through observations of bone mineral density and histomorphometric parameters, ...

Osteoclasts are bone resorbing, multinucleate cells that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursor cells. Although previous studies have revealed important molecular signals, how the bone resorptive functions of such cells are controlled in vivo remains less well characterized. Here, we visualized fluorescently labeled mature osteoclasts in intact mouse ...

Paget's disease of bone is characterized by highly localized areas of increased bone resorption accompanied by exuberant, but aberrant new bone formation with the primary cellular abnormality in osteoclasts. Paget's disease provides an important paradigm for understanding the molecular mechanisms regulating both osteoclast formation and osteoclast-induced osteoblast activity. Both genetic and e...