Regulation of p38 MAPK phosphorylation inhibits chondrocyte apoptosis in response to heat stress or mechanical stress

  • Authors:
    • Ken Takebe
    • Takayuki Nishiyama
    • Shinya Hayashi
    • Shingo Hashimoto
    • Takaaki Fujishiro
    • Noriyuki Kanzaki
    • Kohei Kawakita
    • Kenjiro Iwasa
    • Ryosuke Kuroda
    • Masahiro Kurosaka
  • View Affiliations

  • Published online on: December 22, 2010     https://doi.org/10.3892/ijmm.2010.588
  • Pages: 329-335
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Abstract

Activation of p38 MAPK has been associated with a stress response and with apoptotic processes. However, the function of p38 MAPK in chondrocytes is not clearly understood. In this study, we analyzed the expression of p38 MAPK in chondrocytes and investigated the function of p38 MAPK in response to heat stress and mechanical stress. Chondrocytes were isolated from human cartilage and cultured. Expression of p38 and phosphorylated p38 in cartilage of patients with osteoarthritis (OA) was compared to those in normal cartilage by immunohistochemistry and Western blotting. Human knee chondrocytes were exposed to heat stress or mechanical stress. Normal knee chondrocytes were pre-treated with SB203580 or p38 small interfering RNA (siRNA) before induction of heat stress or mechanical stress. Chondrocyte apoptosis was detected by TUNEL staining and Western blotting of cleaved caspases. OA and normal chondrocytes expressed p38; however, OA chondrocytes showed much higher phosphorylated p38 compared to normal chondrocytes. Heat stress or mechanical stress induced apoptosis and increased phosphorylated p38 in normal chondrocytes. The TUNEL positive cells and expression levels of phosphorylated p38 in response to stress decreased when chondrocytes were incubated with SB203580 or transfected with siRNA against p38. In conclusion, we have demonstrated that heat stress or mechanical stress increased chondrocyte apoptosis via phosphorylation of p38. Stress-induced chondrocyte apoptosis decreased due to inhibition of p38 MAPK activation. In contrast, the phosphorylation of p38 MAPK increased in OA chondrocytes. Our results show that down-regulation of p38 MAPK activation inhibits chondrocyte death induced by heat stress or mechanical stress.

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March 2011
Volume 27 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Takebe K, Nishiyama T, Hayashi S, Hashimoto S, Fujishiro T, Kanzaki N, Kawakita K, Iwasa K, Kuroda R, Kurosaka M, Kurosaka M, et al: Regulation of p38 MAPK phosphorylation inhibits chondrocyte apoptosis in response to heat stress or mechanical stress. Int J Mol Med 27: 329-335, 2011.
APA
Takebe, K., Nishiyama, T., Hayashi, S., Hashimoto, S., Fujishiro, T., Kanzaki, N. ... Kurosaka, M. (2011). Regulation of p38 MAPK phosphorylation inhibits chondrocyte apoptosis in response to heat stress or mechanical stress. International Journal of Molecular Medicine, 27, 329-335. https://doi.org/10.3892/ijmm.2010.588
MLA
Takebe, K., Nishiyama, T., Hayashi, S., Hashimoto, S., Fujishiro, T., Kanzaki, N., Kawakita, K., Iwasa, K., Kuroda, R., Kurosaka, M."Regulation of p38 MAPK phosphorylation inhibits chondrocyte apoptosis in response to heat stress or mechanical stress". International Journal of Molecular Medicine 27.3 (2011): 329-335.
Chicago
Takebe, K., Nishiyama, T., Hayashi, S., Hashimoto, S., Fujishiro, T., Kanzaki, N., Kawakita, K., Iwasa, K., Kuroda, R., Kurosaka, M."Regulation of p38 MAPK phosphorylation inhibits chondrocyte apoptosis in response to heat stress or mechanical stress". International Journal of Molecular Medicine 27, no. 3 (2011): 329-335. https://doi.org/10.3892/ijmm.2010.588