Hydrostatic Pressure Influences HIF-2 Alpha Expression in Chondrocytes

International Journal of Molecular Sciences

Hiroaki Inoue²  Yuji Arai²  Tsunao Kishida¹  Ryu Terauchi²  Kuniaki Honjo²  Shuji Nakagawa²  Shinji Tsuchida²  Tomohiro Matsuki²  Keiichirou Ueshima²  Hiroyoshi Fujiwara²  Osam Mazda¹  Toshikazu Kubo² 

[1] Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan; E-Mails:;Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan; E-Mails:

关键词: hypoxia inducible factor (HIF)-2α;    hydrostatic pressure;    chondrocytes;    hypertrophic differentiation;    osteoarthritis;    cartilage degeneration;    inflammation;   

DOI  :  10.3390/ijms16011043

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.