title: Role of HIF-1α and HIF-2α in osteoarthritis.
abstract: The hallmark of OA is cartilage destruction, several factors such as catabolic enzymes and chondrocyte death include apoptosis and/or autophagy are considered for the pathogenesis. Articular cartilage is maintained in a low oxygen environment throughout life. Chondrocytes are therefore adapted to these hypoxic conditions. The increased HIF-1α and HIF-2α mediate the response of chondrocytes to hypoxia. HIF-1α regulates chondrogenesis by regulating SOX9 expression in the genetic level, HIF-1 also serves to regulate both autophagy and apoptosis. Therefore, HIF-1α may protect articular cartilage by promoting the chondrocyte phenotype, maintaining chondrocyte viability, and supporting metabolic adaptation to a hypoxic environment. In contrast with HIF-1α, HIF-2α is a catabolic factor in the osteoarthritic process. Although HIF-2α is essential for hypoxic induction of the human articular chondrocyte phenotype, HIF-2α directly induces the expression of catabolic factors in chondrocytes, and HIF-2α enhances Fas expression to mediate chondrocyte apoptosis and regulates autophagy in maturing chondrocytes. Taken together, manipulation of HIF-1α and HIF-2α could represent a promising approach to the treatment of OA. Further study should elucidate the exact machnism of HIF-1α and HIF-2α in cartilage and determine which is predominant in osteoarthritic process.
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008 Hunan, China.
authors.forename: Fang-Jie
authors.initials: FJ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008 Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008 Hunan, China. Electronic address: lghxycsu@126.com.
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Lei
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D002358:Cartilage, Articular / Q000502:physiology / Q000503:physiopathology; D019902:Chondrocytes / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D010003:Osteoarthritis / Q000503:physiopathology*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human
keywords: Apoptosis; Autophagy; HIF-1α; HIF-2α; Hypoxia; Osteoarthritis