|
|||||
|
|
Activation of the hypoxia-inducible factor-1 in overloaded temporomandibular joint, and induction of osteoclastogenesis |
|
| Authors: | Maya Shirakura Hidetaka Eguchi Hideaki Nakamura Keiko Hiyama Eiji Tanaka Takashi Takata |
| Affiliation: | a Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan b Department of Translational Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan c Translational Research Center, Saitama Medical University International Medical Center, Saitama, Japan d Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan e Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan f Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden |
| 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-1α (Hif-1α) 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-1α expression was observed specifically in mature and hypertrophic chondrocytes, and Hif-1α-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-1α 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-1α played a role, in part, in its regulation. |
| Keywords: | Temporomandibular joint (TMJ) Osteoarthritis (OA) Chondrocyte Hypoxia-inducible factor-1 (Hif-1) Osteoprotegerin (Opg) |
| 本文献已被 ScienceDirect 等数据库收录！ | |