Open Access

Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation

  • Authors:
    • Jiangbo Yan
    • Dong Ding
    • Gangning Feng
    • Yong Yang
    • Yong Zhou
    • Long Ma
    • Haohui Guo
    • Zhidong Lu
    • Qunhua Jin
  • View Affiliations

  • Published online on: January 17, 2022     https://doi.org/10.3892/etm.2022.11146
  • Article Number: 222
  • Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoarthritis (OA) is an age‑related degenerative disease, and its incidence is increasing with the ageing of the population. Metformin, as the first‑line medication for the treatment of diabetes, has received increasing attention for its role in OA. The purpose of the present study was to confirm the therapeutic effect of metformin in a mouse model of OA and to determine the mechanism underlying the resultant delay in OA progression. The right knees of 8‑week‑old C57BL/6 male mice were subjected to destabilization of the medial meniscus (DMM). Metformin (200 mg/kg) was then administered daily for 4 or 8 weeks. Safranin O‑fast green staining, H&E staining and micro‑CT were used to analyse the structure and morphological changes. Immunohistochemical staining was used to detect type II collagen (Col II), matrix metalloproteinase 13 (MMP‑13), NOD‑like receptor protein 3 (NLRP3), caspase‑1, gasdermin D (GSDMD) and IL‑1β protein expression. Reverse transcription‑quantitative PCR was used to detect the mRNA expression of NLRP3, caspase‑1, GSDMD and IL‑1β. Histomorphological staining showed that metformin delayed the progression of OA in the DMM model. With respect to cartilage, metformin decreased the Osteoarthritis Research Society International score, increased the thickness of hyaline cartilage and decreased the thickness of calcified cartilage. Regarding the mechanism, in cartilage, metformin increased the expression of Col II and decreased the expression of MMP‑13, NLRP3, caspase‑1, GSDMD and IL‑1β. In addition, in subchondral bone, metformin inhibited osteophyte formation, increased the bone volume fraction (%) and the bone mineral density (g/cm3), decreased the trabecular separation (mm) in early stage of osteoarthritis (4 weeks) but the opposite in an advanced stage of osteoarthritis (8 weeks). Overall, metformin inhibited the activation of NLRP3 inflammasome, decreased cartilage degradation, reversed subchondral bone remodelling and inhibited chondrocyte pyroptosis.
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March-2022
Volume 23 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Yan J, Ding D, Feng G, Yang Y, Zhou Y, Ma L, Guo H, Lu Z and Jin Q: Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation. Exp Ther Med 23: 222, 2022
APA
Yan, J., Ding, D., Feng, G., Yang, Y., Zhou, Y., Ma, L. ... Jin, Q. (2022). Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation. Experimental and Therapeutic Medicine, 23, 222. https://doi.org/10.3892/etm.2022.11146
MLA
Yan, J., Ding, D., Feng, G., Yang, Y., Zhou, Y., Ma, L., Guo, H., Lu, Z., Jin, Q."Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation". Experimental and Therapeutic Medicine 23.3 (2022): 222.
Chicago
Yan, J., Ding, D., Feng, G., Yang, Y., Zhou, Y., Ma, L., Guo, H., Lu, Z., Jin, Q."Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation". Experimental and Therapeutic Medicine 23, no. 3 (2022): 222. https://doi.org/10.3892/etm.2022.11146