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Article

Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway

  • Authors:
    • Jiayao Ouyang
    • Huaji Jiang
    • Hang Fang
    • Wenbo Cui
    • Daozhang Cai
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China, Department of Pain, Yue Bei People's Hospital, Shaoguan, Guangdong 512000, P.R. China, Department of Orthopaedics, Dongguan Eighth People's Hospital, Dongguan, Guangdong 523326, P.R. China
  • Pages: 9636-9644
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    Published online on: October 12, 2017
       https://doi.org/10.3892/mmr.2017.7777
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Abstract

Osteoarthritis (OA) is the most common disease of the joints, and is characterized by the breakdown of cartilage and degradation of the extracellular matrix. OA causes a high level of patient suffering and incurs large societal costs; however, the current strategies for treating OA are restricted due to limited understanding of the underlying molecular and cellular mechanisms. In the present study, the beneficial effects of isoimperatorin (Iso) were investigated using an experimental mouse model of OA, and its mechanism of action on primary chondrocytes was elucidated. Destabilization of the medial meniscus was performed on 8‑week‑old male mice to induce OA in the knees. Iso (500 mg/g/day) was intragastrically administered for 4 weeks. Degeneration of articular cartilage was assessed by histology using the Osteoarthritis Research Society International scoring system. The expression of matrix metalloproteinase (MMP)13, Runt‑related transcription factor (Runx)2, type X collagen (Col X) and vascular endothelial growth factor (VEGF) in the knee joints was examined by immunohistochemistry. In vitro, murine primary chondrocytes were treated with various concentrations of Iso, followed by 10 ng/ml interleukin‑1. The mRNA expression levels of MMP13, Runx2, Col X and VEGF were determined by reverse transcription‑quantitative polymerase chain reaction. The levels of autophagy and mammalian target of rapamycin (mTOR) signaling were determined by western blotting. Iso significantly ameliorated the severity of articular cartilage degradation in mice with experimental OA. The expression levels of MMP13, Runx2, Col X and VEGF were reduced in Iso‑treated mice. In murine primary chondrocytes, Iso also reduced MMP13, Runx2, Col X and VEGF expression, and activated autophagy by downregulating the mTOR complex 1 (mTORC1) signaling pathway. Therefore, the results of the present study demonstrated that Iso ameliorates OA‑induced pathological alterations by delaying chondrocyte deterioration, activating autophagy and inhibiting mTORC1, which suggests that Iso may have therapeutic potential for attenuating articular cartilage degradation and treating OA.
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Copy and paste a formatted citation
Spandidos Publications style
Ouyang J, Jiang H, Fang H, Cui W and Cai D: Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway. Mol Med Rep 16: 9636-9644, 2017.
APA
Ouyang, J., Jiang, H., Fang, H., Cui, W., & Cai, D. (2017). Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway. Molecular Medicine Reports, 16, 9636-9644. https://doi.org/10.3892/mmr.2017.7777
MLA
Ouyang, J., Jiang, H., Fang, H., Cui, W., Cai, D."Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway". Molecular Medicine Reports 16.6 (2017): 9636-9644.
Chicago
Ouyang, J., Jiang, H., Fang, H., Cui, W., Cai, D."Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway". Molecular Medicine Reports 16, no. 6 (2017): 9636-9644. https://doi.org/10.3892/mmr.2017.7777
Copy and paste a formatted citation
x
Spandidos Publications style
Ouyang J, Jiang H, Fang H, Cui W and Cai D: Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway. Mol Med Rep 16: 9636-9644, 2017.
APA
Ouyang, J., Jiang, H., Fang, H., Cui, W., & Cai, D. (2017). Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway. Molecular Medicine Reports, 16, 9636-9644. https://doi.org/10.3892/mmr.2017.7777
MLA
Ouyang, J., Jiang, H., Fang, H., Cui, W., Cai, D."Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway". Molecular Medicine Reports 16.6 (2017): 9636-9644.
Chicago
Ouyang, J., Jiang, H., Fang, H., Cui, W., Cai, D."Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway". Molecular Medicine Reports 16, no. 6 (2017): 9636-9644. https://doi.org/10.3892/mmr.2017.7777
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