title: The hypoxia-inducible factor pathway, prolyl hydroxylase domain protein inhibitors, and their roles in bone repair and regeneration.
abstract: 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.
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xiwu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xiwu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Jia
authors.identifier: 0000-0002-5638-8871
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xiwu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Zefeng
authors.identifier: 0000-0002-2908-3490
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xiwu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Xiaoqian
authors.identifier: 0000-0002-5498-6800
authors.initials: X
authors.lastname: Dang
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xiwu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Kunzheng
authors.identifier: 0000-0002-1981-4237
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D064828:Prolyl Hydroxylases / Q000378:metabolism*; D064800:Prolyl-Hydroxylase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D064828:Prolyl Hydroxylases; D064800:Prolyl-Hydroxylase Inhibitors