| First Author | Koide M | Year | 2017 |
| Journal | J Bone Miner Res | Volume | 32 |
| Issue | 10 | Pages | 2074-2086 |
| PubMed ID | 28543818 | Mgi Jnum | J:274935 |
| Mgi Id | MGI:6296511 | Doi | 10.1002/jbmr.3175 |
| Citation | Koide M, et al. (2017) Bone Formation Is Coupled to Resorption Via Suppression of Sclerostin Expression by Osteoclasts. J Bone Miner Res 32(10):2074-2086 |
| abstractText | Bone formation is coupled to bone resorption throughout life. However, the coupling mechanisms are not fully elucidated. Using Tnfrsf11b-deficient (OPG(-/-) ) mice, in which bone formation is clearly coupled to bone resorption, we found here that osteoclasts suppress the expression of sclerostin, a Wnt antagonist, thereby promoting bone formation. Wnt/beta-catenin signals were higher in OPG(-/-) and RANKL-transgenic mice with a low level of sclerostin. Conditioned medium from osteoclast cultures (Ocl-CM) suppressed sclerostin expression in UMR106 cells and osteocyte cultures. In vitro experiments revealed that osteoclasts secreted leukemia inhibitory factor (LIF) and inhibited sclerostin expression. Anti-RANKL antibodies, antiresorptive agents, suppressed LIF expression and increased sclerostin expression, thereby reducing bone formation in OPG(-/-) mice. Taken together, osteoclast-derived LIF regulates bone turnover through sclerostin expression. Thus, LIF represents a target for improving the prolonged suppression of bone turnover by antiresorptive agents. (c) 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. |
