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Hypoxia Signaling in the Skeleton: Implications for Bone Health

  • Skeletal Biology and Regulation (M Forwood and A Robling, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

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.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Acknowledgements

We are grateful to those whose work was cited within and to those whose work was not due to space limitations. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award R01AR064255 (DCG).

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  1. Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA, 95616, USA

    Clare E. Yellowley & Damian C. Genetos

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Yellowley, C.E., Genetos, D.C. Hypoxia Signaling in the Skeleton: Implications for Bone Health. Curr Osteoporos Rep 17, 26–35 (2019). https://doi.org/10.1007/s11914-019-00500-6

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