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Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway

  • Authors:
    • Yongsheng Yang
    • Qiumei Dong
    • Rongheng Li
  • View Affiliations / Copyright

    Affiliations: Department of the Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010000, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 307-316
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    Published online on: December 29, 2016
       https://doi.org/10.3892/ijmm.2016.2843
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Abstract

The induction of apoptosis-resistant rheumatoid synovial tissue cells has been related to constitutively active Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling in rheumatoid arthritis (RA). The excessive proliferation and inherent resistance to apoptosis of fibroblast-like synoviocytes (FLS) is an important mechanism by which RA originates. However, the effects of matrine on FLS in RA is unclear. The present study aimed to investigate the mechanism of action of matrine in a rat model of collagen‑induced arthritis (CIA). The CIA model was established using bovine type II collagen. FLS were isolated from control and CIA rats, cultured in vitro, and confirmed to harbor fibroblast‑like characteristics. After treatment of FLS with varying conc­entrations of matrine, the JAK2 inhibitor AG490, or a combination of both drugs, cell proliferation, apoptosis rate, expression of apoptotic markers and the activation of the JAK/STAT pathway were assessed. Additionally, CIA rats were administered either matrine or methotrexate by oral gavage to examine the effects of therapeutic intervention on arthritis pathogenesis. The arthritis index (AI) was measured and ankle joint structure was analyzed histologically to determine the severity of CIA. Furthermore, expression levels of apoptotic markers and members of the JAK/STAT family were also examined in vivo. Compared with the CIA group, matrine reduced AI and improved ankle pathology. Matrine also inhibited FLS proliferation, induced G0/G1 cell cycle arrest, and increased the rate of apoptosis in vitro. The effects of matrine on apoptosis induction were further confirmed by observations that Bcl-2 levels were decreased, whereas Bax and caspase-3 levels were increased in the matrine-treated synovial tissues and FLS. Finally, matrine treatment also diminished the phosphorylation, and hence activation of JAK2, STAT1 and STAT3. Our results suggest that matrine induces the apoptosis of FLS from rats with CIA by inhibiting activation of the JAK/STAT signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Yang Y, Dong Q and Li R: Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway. Int J Mol Med 39: 307-316, 2017.
APA
Yang, Y., Dong, Q., & Li, R. (2017). Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway. International Journal of Molecular Medicine, 39, 307-316. https://doi.org/10.3892/ijmm.2016.2843
MLA
Yang, Y., Dong, Q., Li, R."Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway". International Journal of Molecular Medicine 39.2 (2017): 307-316.
Chicago
Yang, Y., Dong, Q., Li, R."Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway". International Journal of Molecular Medicine 39, no. 2 (2017): 307-316. https://doi.org/10.3892/ijmm.2016.2843
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Y, Dong Q and Li R: Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway. Int J Mol Med 39: 307-316, 2017.
APA
Yang, Y., Dong, Q., & Li, R. (2017). Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway. International Journal of Molecular Medicine, 39, 307-316. https://doi.org/10.3892/ijmm.2016.2843
MLA
Yang, Y., Dong, Q., Li, R."Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway". International Journal of Molecular Medicine 39.2 (2017): 307-316.
Chicago
Yang, Y., Dong, Q., Li, R."Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway". International Journal of Molecular Medicine 39, no. 2 (2017): 307-316. https://doi.org/10.3892/ijmm.2016.2843
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