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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.
AuthorsMaya Shirakura, Keiji Tanimoto, Hidetaka Eguchi, Mutsumi Miyauchi, Hideaki Nakamura, Keiko Hiyama, Kotaro Tanimoto, Eiji Tanaka, Takashi Takata, Kazuo Tanne
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 393 Issue 4 Pg. 800-5 (Mar 19 2010) ISSN: 1090-2104 [Electronic] United States
PMID20171183 (Publication Type: Journal Article)
CopyrightCopyright 2010 Elsevier Inc. All rights reserved.
Chemical References
  • Hypoxia-Inducible Factor 1, alpha Subunit
Topics
  • Animals
  • Bone Resorption (metabolism, pathology)
  • Cartilage, Articular (metabolism, pathology)
  • Chondrocytes (metabolism, pathology)
  • Disease Models, Animal
  • Hypoxia-Inducible Factor 1, alpha Subunit (agonists, biosynthesis)
  • Male
  • Osteoarthritis (metabolism, pathology)
  • Osteoclasts (metabolism, pathology)
  • Rats
  • Rats, Wistar
  • Temporomandibular Joint Disorders (metabolism, pathology)

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