Regulation of the differentiation and function of osteoclasts

Chambers, T.J.

doi:10.1002/1096-9896(2000)9999:9999<::aid-path645>3.0.co;2-q

Cited by 275 publications

(75 citation statements)

References 134 publications

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“…It is very likely that these processes are separately regulated. However, although there have been considerable advances in our understanding of the mechanisms through which the differentiation of osteoclasts is regulated [1][2][3], much less is known of the mechanisms that modulate their function.…”

Section: Introductionmentioning

confidence: 53%

Regulation and enzymatic basis of bone resorption by human osteoclasts

2007

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Although much has been learned recently of the mechanisms that regulate osteoclastic differentiation, much less is known of the means through which their resorptive activity is controlled. This is especially so for human osteoclasts. We have recently developed an assay that allows us to measure resorptive activity while minimizing confounding effects on differentiation by optimizing osteoclastogenesis, so that measurable resorption occurs over a short period, and by relating resorption in each culture during the test period to the resorption that had occurred in the same culture in a prior control period. In the present study, we found that RANKL (receptor activator of nuclear factor kappaB ligand) strongly stimulated the release of CTX-I (C-terminal telopeptide degradation product of type I collagen) by osteoclasts over a similar range to that over which it induces osteoclastic differentiation, consistent with a distinct action on osteoclastic function. CT (calcitonin) dose-dependently inhibited bone resorption, whereas PTH (parathyroid hormone), IL (interleukin)-1, TNF-alpha (tumour necrosis factor-alpha), IL-6, IL-8, VEGF (vascular endothelial growth factor), MCP-1 (monocyte chemoattractant protein-1), MIP-1gamma (macrophage inflammatory protein-1gamma), IFN (interferon)-gamma and dibutyryl cGMP had no significant effect. Ca(2+), cyclosporin A, IFN-beta and dibutyryl cAMP all strongly suppressed resorption. Bone resorption was also strongly suppressed by alendronate, the cysteine protease inhibitor E64 and the cathepsin K inhibitor MV061194. Inhibitors of MMPs (matrix metalloproteinases) had no effect on CTX-I release. Moreover, the release of the MMP-derived collagen fragment ICTP (C-terminal cross-linked telopeptide of type I collagen) represented less that 0.01% of the quantity of CTX-I released in our cultures. This suggests that MMPs make, at most, a very small contribution to the bone-resorptive activity of osteoclasts.

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Section: Introductionmentioning

confidence: 53%

Regulation and enzymatic basis of bone resorption by human osteoclasts

2007

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“…Dynamic histomorphometric analysis clearly demonstrated that ovariectomized LysM.Rac1 KO samples had lower bone formation rates compared to WT, which is the expected consequence of decreased osteoclast activity [35,36] in the osteoclast-osteoblast coupling paradigm. We speculate that the reduced osteoclast activity in the LysM.…”

Section: Osteoporosis-induced Rac Knock-out Mouse Modelmentioning

confidence: 99%

Deleting Rac1 improves vertebral bone quality and resistance to fracture in a murine ovariectomy model

et al. 2010

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“…RANKL is a critical factor inducing osteoclast differentiation. It is secreted by osteoblasts and its action on osteoclasts is antagonized by a soluble receptor called osteoprotegerin (OPG) [100,101]. Mice deficient for Rankl are severely osteopetrotic due to the lack of osteoclasts and the absence of bone resorption [102].…”

Section: Beta-adrenergic Signaling In Osteoblasts Increases Bone Resomentioning

confidence: 99%

Neuronal signaling and the regulation of bone remodeling

Elefteriou

2005

Cell. Mol. Life Sci.

106

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An increasing number of studies suggest that nerve-derived signals play an important role in the regulation of bone remodeling. Neuropeptides and receptors/transporters of adrenergic, glutaminergic, serotoninergic, dopaminergic and sensory nature have been described in osteoblasts in vitro. Downstream signaling pathways and targets genes have been identified, but the in vivo relevance of these findings remained controversial until more recent gene gain and loss of function studies confirmed the role of CGRP and beta2-adrenergic receptor signaling in osteoblasts. Tissue and time-conditional mutant mice originally generated for studies unrelated to bone are now available tools to determine the role of neuronal signaling in bone and to dissociate the central and peripheral role of these signals. Lastly, understanding how the central nervous system integrates homeostatic signals with the regulation of bone homeostasis will be the next exciting subject of research in the field.

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Regulation of the differentiation and function of osteoclasts

Cited by 275 publications

References 134 publications

Regulation and enzymatic basis of bone resorption by human osteoclasts

Regulation and enzymatic basis of bone resorption by human osteoclasts

Deleting Rac1 improves vertebral bone quality and resistance to fracture in a murine ovariectomy model

Neuronal signaling and the regulation of bone remodeling

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