title: Activation of the hypoxia-inducible factor-1 in overloaded temporomandibular joint, and induction of osteoclastogenesis.
abstract: Vascular endothelial growth factor (Vegf) was previously shown to be expressed specifically in the condylar cartilage of temporomandibular joint-osteoarthritis (TMJ-OA) model rats. Here we demonstrate for the first time that hypoxia-inducible factor-1alpha (Hif-1alpha) is activated in mature chondrocytes of temporomandibular joint-osteoarthritis (TMJ-OA) model rat by mechanical overload, and that activated Hif-1 in chondrocytes can induce osteoclastogenesis via repression of osteoprotegerin (Opg) expression. In rat TMJs, degeneration of the condylar cartilage became prominent in proportion to the duration of overloading. Hif-1alpha expression was observed specifically in mature and hypertrophic chondrocytes, and Hif-1alpha-positivity, level of Vegf expression, and tartrate-resistant acid phosphatase (TRAP)-positive cell numbers all increased in the same manner. When ATDC5 cells induced differentiation by insulin were cultured under hypoxia, Hif-1alpha induction was observed in mature stage, but not in immature stage. Inductions of Hif-1-target genes showed a similar expression pattern. In addition, expression of Opg decreased in hypoxia, and Hif-1alpha played a role, in part, in its regulation.
authors.affiliation: Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Shirakura
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Eguchi
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Miyauchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Keiko
authors.initials: K
authors.lastname: Hiyama
authors.forename: Kotaro
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanne
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000819:agonists* / Q000096:biosynthesis; D008297:Male; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013705:Temporomandibular Joint Disorders / Q000378:metabolism / Q000473:pathology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit