Open Access

Histone deacetylase-4 and histone deacetylase-8 regulate interleukin-1β-induced cartilage catabolic degradation through MAPK/JNK and ERK pathways

  • Authors:
    • Pengcheng Wang
    • Zekai Mao
    • Qiyong Pan
    • Rui Lu
    • Xiaojian Huang
    • Xiaobin Shang
    • Rui Zhang
    • Hongbo You
  • View Affiliations

  • Published online on: January 22, 2018     https://doi.org/10.3892/ijmm.2018.3410
  • Pages: 2117-2127
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interleukin-1β (IL-1β)-induced inflammatory response is associated with osteoarthritis (OA) and its development. Histone deacetylase (HDAC) may be involved in regulating this pathogenesis, but the mechanism has yet to be elucidated. The aim of the present study was to investigate the mechanism underlying the regulation of IL‑1β‑stimulated catabolic degradation of cartilage by HDAC. An in vitro model of OA was generated using rat articular chondrocytes (rACs) treated with IL‑1β. The role of HDAC in IL‑1β‑induced gene expression was investigated using HDAC inhibitors and specific small interfering RNAs (siRNAs). The association of diverse mitogen‑activated protein kinase (MAPK) pathways was examined. The IL‑1β‑induced expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)‑4 and ADAMTS‑5, and the production of collagen X and cyclooxygenase‑2 in rACs was accompanied by the expression of HDAC4 and HDAC8, and were significantly downregulated by HDAC inhibitors and specific siRNAs. IL‑1β‑induced activation of extracellular signal‑regulated kinase was downregulated by the HDAC inhibitor Trichostatin A, but not significantly by PCI‑34051. The activation of c‑Jun N‑terminal kinase was observably downregulated by the latter, but only slightly by the former. These results suggest that HDAC4 and HDAC8 may serve as key upstream mediators of MAPK in regulating the IL‑1β‑induced cartilage catabolic and degradation. Therefore, inhibiting HDAC4 or HDAC8 or both may be a promising therapeutic strategy in preventing and treating OA.
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April-2018
Volume 41 Issue 4

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

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Spandidos Publications style
Wang P, Mao Z, Pan Q, Lu R, Huang X, Shang X, Zhang R and You H: Histone deacetylase-4 and histone deacetylase-8 regulate interleukin-1β-induced cartilage catabolic degradation through MAPK/JNK and ERK pathways. Int J Mol Med 41: 2117-2127, 2018
APA
Wang, P., Mao, Z., Pan, Q., Lu, R., Huang, X., Shang, X. ... You, H. (2018). Histone deacetylase-4 and histone deacetylase-8 regulate interleukin-1β-induced cartilage catabolic degradation through MAPK/JNK and ERK pathways. International Journal of Molecular Medicine, 41, 2117-2127. https://doi.org/10.3892/ijmm.2018.3410
MLA
Wang, P., Mao, Z., Pan, Q., Lu, R., Huang, X., Shang, X., Zhang, R., You, H."Histone deacetylase-4 and histone deacetylase-8 regulate interleukin-1β-induced cartilage catabolic degradation through MAPK/JNK and ERK pathways". International Journal of Molecular Medicine 41.4 (2018): 2117-2127.
Chicago
Wang, P., Mao, Z., Pan, Q., Lu, R., Huang, X., Shang, X., Zhang, R., You, H."Histone deacetylase-4 and histone deacetylase-8 regulate interleukin-1β-induced cartilage catabolic degradation through MAPK/JNK and ERK pathways". International Journal of Molecular Medicine 41, no. 4 (2018): 2117-2127. https://doi.org/10.3892/ijmm.2018.3410