| First Author | Riddle RC | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 52 | Pages | 44449-56 |
| PubMed ID | 22081627 | Mgi Jnum | J:178824 |
| Mgi Id | MGI:5300390 | Doi | 10.1074/jbc.M111.276683 |
| Citation | Riddle RC, et al. (2011) Hypoxia-inducible Factor-1alpha Protein Negatively Regulates Load-induced Bone Formation. J Biol Chem 286(52):44449-56 |
| abstractText | Mechanical loads induce profound anabolic effects in the skeleton, but the molecular mechanisms that transduce such signals are still poorly understood. In this study, we demonstrate that the hypoxia-inducible factor-1alpha (Hif-1alpha) is acutely up-regulated in response to exogenous mechanical stimuli secondary to prostanoid signaling and Akt/mTOR (mammalian target of rapamycin) activation. In this context, Hif-1alpha associates with beta-catenin to inhibit Wnt target genes associated with bone anabolic activity. Mice lacking Hif-1alpha in osteoblasts and osteocytes form more bone when subjected to tibia loading as a result of increased osteoblast activity. Taken together, these studies indicate that Hif-1alpha serves as a negative regulator of skeletal mechanotransduction to suppress load-induced bone formation by altering the sensitivity of osteoblasts and osteocytes to mechanical signals. |
