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Wnt/β‑catenin signaling may induce senescence of chondrocytes in osteoarthritis

  • Authors:
    • Weijun Li
    • Yan Xiong
    • Weiping Chen
    • Lidong Wu
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2631-2638
    |
    Published online on: July 17, 2020
       https://doi.org/10.3892/etm.2020.9022
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Abstract

Osteoarthritis (OA) is an autoimmune disease associated with increasing age. Typically, chondrocyte senescence is believed to serve an important role in the development and progression of OA. However, the specific mechanisms underlying chondrocyte senescence have not been fully addressed. The present study hypothesized that the Wnt/β‑catenin signaling may represent a major regulator of chondrocyte senescence. In addition, the acetylated levels of p53 and sirtuin‑1 (SIRT‑1) were examined as putative markers for chondrocyte senescence, since activation of p53 is considered an important step in the regulation of senescence. The Wnt/β‑catenin signaling pathway was activated using LiCl and inhibited using the Wnt signaling pathway inhibitor, dickkopf‑1 (DKK1) in order to evaluate the role of this pathway in the development of OA. Senescent cells were detected using the senescence‑associated indicator acidic senescence‑associated β‑galactosidase (SA‑β‑gal). The effects of p53 and p16 on chondrocyte senescence were assessed via activation of Wnt/β‑catenin signaling using Wnt‑1. In addition, β‑catenin was transfected into chondrocytes to induce activation of the Wnt/β‑catenin signaling pathway. Finally, a rabbit model of OA was used to assess whether the observed effects on the Wnt/β‑catenin signaling pathway and the induction of chondrocyte senescence were perpetuated. Activation of Wnt/β‑catenin signaling increased the expression levels of SA‑β‑gal, p53, p16 and acetylated p53. Transfection of β‑catenin in chondrocytes increased the expression levels of acetylated p53 and decreased the expression levels of SIRT‑1, which in turn deacetylated p53 and modulated its activity. Finally, the role of the Wnt/β‑catenin signaling pathway was confirmed in the development of OA using a rabbit model with this condition. The present study suggested that activation of the Wnt/β‑catenin signaling pathway promoted chondrocyte senescence, through downregulation of SIRT‑1 and increased the expression of acetylated p53.
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Copy and paste a formatted citation
Spandidos Publications style
Li W, Xiong Y, Chen W and Wu L: Wnt/β‑catenin signaling may induce senescence of chondrocytes in osteoarthritis. Exp Ther Med 20: 2631-2638, 2020.
APA
Li, W., Xiong, Y., Chen, W., & Wu, L. (2020). Wnt/β‑catenin signaling may induce senescence of chondrocytes in osteoarthritis. Experimental and Therapeutic Medicine, 20, 2631-2638. https://doi.org/10.3892/etm.2020.9022
MLA
Li, W., Xiong, Y., Chen, W., Wu, L."Wnt/β‑catenin signaling may induce senescence of chondrocytes in osteoarthritis". Experimental and Therapeutic Medicine 20.3 (2020): 2631-2638.
Chicago
Li, W., Xiong, Y., Chen, W., Wu, L."Wnt/β‑catenin signaling may induce senescence of chondrocytes in osteoarthritis". Experimental and Therapeutic Medicine 20, no. 3 (2020): 2631-2638. https://doi.org/10.3892/etm.2020.9022
Copy and paste a formatted citation
x
Spandidos Publications style
Li W, Xiong Y, Chen W and Wu L: Wnt/β‑catenin signaling may induce senescence of chondrocytes in osteoarthritis. Exp Ther Med 20: 2631-2638, 2020.
APA
Li, W., Xiong, Y., Chen, W., & Wu, L. (2020). Wnt/β‑catenin signaling may induce senescence of chondrocytes in osteoarthritis. Experimental and Therapeutic Medicine, 20, 2631-2638. https://doi.org/10.3892/etm.2020.9022
MLA
Li, W., Xiong, Y., Chen, W., Wu, L."Wnt/β‑catenin signaling may induce senescence of chondrocytes in osteoarthritis". Experimental and Therapeutic Medicine 20.3 (2020): 2631-2638.
Chicago
Li, W., Xiong, Y., Chen, W., Wu, L."Wnt/β‑catenin signaling may induce senescence of chondrocytes in osteoarthritis". Experimental and Therapeutic Medicine 20, no. 3 (2020): 2631-2638. https://doi.org/10.3892/etm.2020.9022
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