| First Author | Takarada T | Year | 2017 |
| Journal | J Bone Miner Res | Volume | 32 |
| Issue | 4 | Pages | 872-881 |
| PubMed ID | 27925286 | Mgi Jnum | J:322667 |
| Mgi Id | MGI:6869501 | Doi | 10.1002/jbmr.3053 |
| Citation | Takarada T, et al. (2017) Bone Resorption Is Regulated by Circadian Clock in Osteoblasts. J Bone Miner Res 32(4):872-881 |
| abstractText | We have previously shown that endochondral ossification is finely regulated by the Clock system expressed in chondrocytes during postnatal skeletogenesis. Here we show a sophisticated modulation of bone resorption and bone mass by the Clock system through its expression in bone-forming osteoblasts. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and Period1 (Per1) were expressed with oscillatory rhythmicity in the bone in vivo, and circadian rhythm was also observed in cultured osteoblasts of Per1::luciferase transgenic mice. Global deletion of murine Bmal1, a core component of the Clock system, led to a low bone mass, associated with increased bone resorption. This phenotype was recapitulated by the deletion of Bmal1 in osteoblasts alone. Co-culture experiments revealed that Bmal1-deficient osteoblasts have a higher ability to support osteoclastogenesis. Moreover, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ]-induced receptor activator of nuclear factor kappaB ligand (Rankl) expression was more strongly enhanced in both Bmal1-deficient bone and cultured osteoblasts, whereas overexpression of Bmal1/Clock conversely inhibited it in osteoblasts. These results suggest that bone resorption and bone mass are regulated at a sophisticated level by osteoblastic Clock system through a mechanism relevant to the modulation of 1,25(OH)2 D3 -induced Rankl expression in osteoblasts. (c) 2017 American Society for Bone and Mineral Research. |
