Hypoxia-inducible factor-1α protein negatively regulates load-induced bone formation

Ryan C. Riddle, Julie M. Leslie, Ted S. Gross, Thomas L. Clemens

Research output: Contribution to journalArticlepeer-review


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-1α (Hif-1α) 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-1α associates with β-catenin to inhibit Wnt target genes associated with bone anabolic activity. Mice lacking Hif-1α 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-1α 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.

Original languageEnglish (US)
Pages (from-to)44449-44456
Number of pages8
JournalJournal of Biological Chemistry
Issue number52
StatePublished - Dec 30 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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