The Hypoxia-Inducible Factor Pathway, Prolyl Hydroxylase Domain Protein Inhibitors, and Their Roles in Bone Repair and Regeneration

Hypoxia-inducible factors (HIFs) are oxygen-dependent transcriptional activators that play crucial roles in angiogenesis, erythropoiesis, energy metabolism, and cell fate decisions. The group of enzymes that can catalyse the hydroxylation reaction of HIF-1 is prolyl hydroxylase domain proteins (PHDs...

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Bibliographic Details
Published in:BioMed research international 2014-01, Vol.2014 (2014), p.1-11
Main Authors: Dang, Xiaoqian, Li, Jia, Yu, Zefeng, Wang, Kunzheng, Fan, Lihong
Format: Article
Language:English
Subjects:
Animals
Basic Helix-Loop-Helix Transcription Factors - metabolism
Bone and Bones - drug effects
Bone and Bones - physiology
Bone Development - drug effects
Bone Development - physiology
Bone regeneration
Bone Regeneration - drug effects
Bone Regeneration - physiology
Enzyme inhibitors
Enzymes
Health aspects
Humans
Insulin-like growth factors
Kinases
Medical research
Medicine, Experimental
Nitric oxide
Prolyl Hydroxylases - metabolism
Prolyl-Hydroxylase Inhibitors - pharmacology
Review
Rodents
Signal Transduction - drug effects
Signal Transduction - physiology
Stem cells
Transcriptional coactivators
Vascular endothelial growth factor
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Summary:Hypoxia-inducible factors (HIFs) are oxygen-dependent transcriptional activators that play crucial roles in angiogenesis, erythropoiesis, energy metabolism, and cell fate decisions. The group of enzymes that can catalyse the hydroxylation reaction of HIF-1 is prolyl hydroxylase domain proteins (PHDs). PHD inhibitors (PHIs) activate the HIF pathway by preventing degradation of HIF-α via inhibiting PHDs. Osteogenesis and angiogenesis are tightly coupled during bone repair and regeneration. Numerous studies suggest that HIFs and their target gene, vascular endothelial growth factor (VEGF), are critical regulators of angiogenic-osteogenic coupling. In this brief perspective, we review current studies about the HIF pathway and its role in bone repair and regeneration, as well as the cellular and molecular mechanisms involved. Additionally, we briefly discuss the therapeutic manipulation of HIFs and VEGF in bone repair and bone tumours. This review will expand our knowledge of biology of HIFs, PHDs, PHD inhibitors, and bone regeneration, and it may also aid the design of novel therapies for accelerating bone repair and regeneration or inhibiting bone tumours.
ISSN:2314-6133
2314-6141
DOI:10.1155/2014/239356