Open Access

Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis

  • Authors:
    • Ni-Tao Cheng
    • Hai Meng
    • Li-Feng Ma
    • Liang Zhang
    • Hao-Miao Yu
    • Zhen-Zhong Wang
    • Ai Guo
  • View Affiliations

  • Published online on: March 23, 2017     https://doi.org/10.3892/ijmm.2017.2934
  • Pages: 1224-1232
  • Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Accumulating evidence suggests that autophagy is closely related to the pathogenesis of osteoarthritis (OA). The aim of this study was to determine the changes in autophagy during the progression of OA and to elucidate the specific role of autophagy in OA. For this purpose, a cellular model of OA was generated by stimulating SW1353 cells with interleukin (IL)-1β and a rabbit model of OA was also established by an intra-articular injection of collagenase, followed by treatment with the autophagy specific inhibitor, 3-methyladenine (3-MA). Cell viability was analyzed by MTS assay, and the mRNA expression levels of matrix metalloproteinases (MMP)-13 and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by RT-qPCR. Cartilage degeneration was examined under a light microscope, and autophagosome and chondrocyte degeneration was observed by transmission electron microscopy. The protein expression of Beclin-1 and light chain 3 (LC3)B was evaluated by western blot analysis and immunofluorescence staining. We found that the autophagy was enhanced during the early stages and was weakened during the late stages of experimental OA. The inhibition of autophagy by 3-MA significantly aggravated the degeneration of chondrocytes and cartilage in experimental OA. Our results thus determine the changes in autophagy during different stages of OA, as well as the role of impaired autophagy in the development of OA. Our data suggest that the regulation of autophagy may be a potential therapeutic strategy with which to attenuate OA.
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May-2017
Volume 39 Issue 5

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

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Spandidos Publications style
Cheng N, Meng H, Ma L, Zhang L, Yu H, Wang Z and Guo A: Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis. Int J Mol Med 39: 1224-1232, 2017.
APA
Cheng, N., Meng, H., Ma, L., Zhang, L., Yu, H., Wang, Z., & Guo, A. (2017). Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis. International Journal of Molecular Medicine, 39, 1224-1232. https://doi.org/10.3892/ijmm.2017.2934
MLA
Cheng, N., Meng, H., Ma, L., Zhang, L., Yu, H., Wang, Z., Guo, A."Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis". International Journal of Molecular Medicine 39.5 (2017): 1224-1232.
Chicago
Cheng, N., Meng, H., Ma, L., Zhang, L., Yu, H., Wang, Z., Guo, A."Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis". International Journal of Molecular Medicine 39, no. 5 (2017): 1224-1232. https://doi.org/10.3892/ijmm.2017.2934