Open Access

The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation

  • Authors:
    • Zhiyong Shu
    • Xiaogang Miao
    • Tainhua Tang
    • Peng Zhan
    • Langqing Zeng
    • Yuwen Jiang
  • View Affiliations

  • Published online on: January 9, 2020     https://doi.org/10.3892/ijmm.2020.4460
  • Pages: 769-778
  • Copyright: © Shu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Knee osteoarthritis (KOA) is a common joint disease with a high incidence rate among middle‑aged and elderly individuals. However, the precise underlying pathological mechanisms and effective treatment of this disease remain to be determined. To explore the effect of high mobility group box 1 (HMGB1) on chondrocyte apoptosis and catabolism, the ATDC5 cell line was cultured as an in vitro model for cartilage research. Cultured cells were treated with recombinant HMGB1 at different concentrations. Hoechst staining and flow cytometry demonstrated that HMGB1 administration significantly induced apoptosis of ATDC5 cells, which was the same as the effect of interleukin‑1β treatment. HMGB1 also induced cartilage matrix degradation, as shown by Alcian blue staining. Moreover, HMGB1 markedly upregulated the expression levels of matrix metallopeptidases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), while genetic silencing of HMGB1 significantly suppressed their expressions. The glycogen synthase kinase (GSK)‑3β/β‑catenin pathway was activated upon HMGB1 treatment. Pharmacological inhibitors or HMGB1 knockdown inactivated the GSK‑3β/β‑catenin pathway, inhibited the expression levels of downstream genes, including MMPs and ADAMTS, and attenuated the apoptosis of ATDC5 cells. Furthermore, the data demonstrated that HMGB1 promoted chondrocyte dysfunction via the regulation of estrogen sulfotransferase and Runt‑related transcription factor 2. Thus, the findings of the present study demonstrated that HMGB1 induces chondrocyte cell apoptosis via activation of GSK‑3β/β‑catenin and the subsequent expression of multiple targeted genes.
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March 2020
Volume 45 Issue 3

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

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APA
Shu, Z., Miao, X., Tang, T., Zhan, P., Zeng, L., & Jiang, Y. (2020). The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation. International Journal of Molecular Medicine, 45, 769-778. https://doi.org/10.3892/ijmm.2020.4460
MLA
Shu, Z., Miao, X., Tang, T., Zhan, P., Zeng, L., Jiang, Y."The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation". International Journal of Molecular Medicine 45.3 (2020): 769-778.
Chicago
Shu, Z., Miao, X., Tang, T., Zhan, P., Zeng, L., Jiang, Y."The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation". International Journal of Molecular Medicine 45, no. 3 (2020): 769-778. https://doi.org/10.3892/ijmm.2020.4460