title: Hydrostatic pressure influences HIF-2 alpha expression in chondrocytes.
abstract: Hypoxia-inducible factor (HIF)-2α is considered to play a major role in the progression of osteoarthritis. Recently, it was reported that pressure amplitude influences HIF-2α expression in murine endothelial cells. We examined whether hydrostatic pressure is involved in expression of HIF-2α in articular chondrocytes. Chondrocytes were cultured and stimulated by inflammation or hydrostatic pressure of 0, 5, 10, or 50 MPa. After stimulation, heat shock protein (HSP) 70, HIF-2α, nuclear factor kappa B (NF-κB), matrix metalloproteinase (MMP)-13, MMP-3, and vascular endothelial growth factor (VEGF) gene expression were evaluated. The levels of all gene expression were increased by inflammatory stress. When chondrocytes were exposed to a hydrostatic pressure of 5 MPa, HIF-2α, MMP-13, and MMP-3 gene expression increased significantly although those of HSP70 and NF-κB were not significantly different from the control group. In contrast, HIF-2α gene expression did not increase under a hydrostatic pressure of 50 MPa although HSP70 and NF-κB expression increased significantly compared to control. We considered that hydrostatic pressure of 5 MPa could regulate HIF-2α independent of NF-κB, because the level of HIF-2α gene expression increased significantly without upregulation of NF-κB expression at 5 MPa. Hydrostatic pressure may influence cartilage degeneration, inducing MMP-13 and MMP-3 expression through HIF-2α.
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. hinoue@koto.kpu-m.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. yarai89046@nike.eonet.ne.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. tsunao@koto.kpu-m.ac.jp.
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. ryutel@mbox.kyoto-inet.or.jp.
authors.forename: Ryu
authors.initials: R
authors.lastname: Terauchi
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. kuniakih@koto.kpu-m.ac.jp.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Honjo
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. shushi@koto.kpu-m.ac.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. tuchi-kf@koto.kpu-m.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tsuchida
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. tmatsuki@koto.kpu-m.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuki
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. ueshima@koto.kpu-m.ac.jp.
authors.forename: Keiichirou
authors.initials: K
authors.lastname: Ueshima
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. fjwr@koto.kpu-m.ac.jp.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. mazda@koto.kpu-m.ac.jp.
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. tkubo@koto.kpu-m.ac.jp.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kubo
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006874:Hydrostatic Pressure; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018840:HSP70 Heat-Shock Proteins; D053583:Interleukin-1beta; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1