Hypoxia Signaling in the Skeleton: Implications for Bone Health

• Published in: Current osteoporosis reports 2019-02, Vol.17 (1), p.26-35
• Main Authors: Yellowley, Clare E., Genetos, Damian C.
• Format: Article
• Language: English
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Bone and Bones - metabolism; Bone Density - physiology; Bone Regeneration - physiology; Epidemiology; Humans; Hypoxia - metabolism; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Medicine; Medicine & Public Health; Mice; Neovascularization, Physiologic - physiology; Orthopedics; Osteocytes - metabolism; Osteogenesis - physiology; Oxygen - metabolism; Section Editors; Skeletal Biology and Regulation (M Forwood and A Robling; Topical Collection on Skeletal Biology and Regulation; Wnt Signaling Pathway - physiology
• ISSN: 1544-1873; 1544-2241
• DOI: 10.1007/s11914-019-00500-6

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.