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A factor that couples bone formation to bone resorption
DOI:10.1038/bonekey.2013.224
Takeshita et al. set out to find a factor to provide the crucial link between bone formation and bone resorption by analyzing the genes expressed during the differentiation of osteoclasts in mice. Mouse genome arrays enabled one transcript to be picked out from 39 000 that met the predefined criteria that were predicted to characterize the factor.
The transcript identified corresponded with the gene collagen triple helix repeat containing 1 (Cthrc1), which is produced by mature osteoclasts. Expression of the Cthrc1 gene was induced in cell culture by contact with hydroxyapatite or dentin. Increasing the concentration of extracellular calcium and phosphate caused an increase in gene expression. The protein was able to stimulate osteoblast differentiation (and therefore bone formation) by interacting with stromal/osteoblastic cells.
Cthrc1 expression was found to be reduced in response to aging or treatment with alendronate (which suppress bone turnover) and was increased in vivo in bone tissue in a state of high turnover (induced by RANKL injections in a mouse model). Osteoclast-specific Cthrc1 deletion caused osteopenia due to an impaired coupling response to bone resorption.
Editor’s comment: This is the first report to identify a factor responsible for coupling bone formation to bone resorption. Identification of its receptor(s) and signaling pathway may lead to a novel therapeutic approach to bone diseases with impaired bone remodeling.
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