Activation of the hypoxia-inducible factor-1 in overloaded temporomandibular joint, and induction of osteoclastogenesis.
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.
Shirakura
Maya
M
Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Tanimoto
Keiji
K
Eguchi
Hidetaka
H
Miyauchi
Mutsumi
M
Nakamura
Hideaki
H
Hiyama
Keiko
K
Tanimoto
Kotaro
K
Tanaka
Eiji
E
Takata
Takashi
T
Tanne
Kazuo
K
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*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit