Hypoxia Signaling in the Skeleton: Implications for Bone Health

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations


Purpose of Review: We reviewed recent literature on oxygen sensing in osteogenic cells and its contribution to development of a skeletal phenotype, the coupling of osteogenesis with angiogenesis and integration of hypoxia into canonical Wnt signaling, and opportunities to manipulate oxygen sensing to promote skeletal repair. Recent Findings: Oxygen sensing in osteocytes can confer a high bone mass phenotype in murine models; common and unique targets of HIF-1α and HIF-2α and lineage-specific deletion of oxygen sensing machinery suggest differentia utilization and requirement of HIF-α proteins in the differentiation from mesenchymal stem cell to osteoblast to osteocyte; oxygen-dependent but HIF-α-independent signaling may contribute to observed skeletal phenotypes. Summary: Manipulating oxygen sensing machinery in osteogenic cells influences skeletal phenotype through angiogenesis-dependent and angiogenesis-independent pathways and involves HIF-1α, HIF-2α, or both proteins. Clinically, an FDA-approved iron chelator promotes angiogenesis and osteogenesis, thereby enhancing the rate of fracture repair.

Original languageEnglish (US)
Pages (from-to)26-35
Number of pages10
JournalCurrent Osteoporosis Reports
Issue number1
StatePublished - Feb 15 2019


  • Bone
  • HIF
  • Hypoxia
  • Sclerostin
  • Wnt

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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