Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair

Int J Mol Sci. 2022 Sep 23;23(19):11201. doi: 10.3390/ijms231911201.

Abstract

Sufficient oxygen is required to maintain normal cellular and physiological function, such as a creature's development, breeding, and homeostasis. Lately, some researchers have reported that both pathological hypoxia and environmental hypoxia might affect bone health. Adaptation to hypoxia is a pivotal cellular event in normal cell development and differentiation and in pathological settings such as ischemia. As central mediators of homeostasis, hypoxia-inducible transcription factors (HIFs) can allow cells to survive in a low-oxygen environment and are essential for the regulation of osteogenesis and skeletal repair. From this perspective, we summarized the role of HIF-1 and HIF-2 in signaling pathways implicated in bone development and skeletal repair and outlined the molecular mechanism of regulation of downstream growth factors and protein molecules such as VEGF, EPO, and so on. All of these present an opportunity for developing therapies for bone regeneration.

Keywords: erythropoietin; hypoxia-inducible factors; osteogenesis; vascular endothelial growth factors; wnt.

Publication types

  • Review

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Humans
  • Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Osteogenesis* / physiology
  • Oxygen / metabolism
  • Transcription Factors / metabolism
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Oxygen