TY - JOUR AB - 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. AD - 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 AU - Ouyang,Jiayao AU - Jiang,Huaji AU - Fang,Hang AU - Cui,Wenbo AU - Cai,Daozhang DA - 2017/12/01 DO - 10.3892/mmr.2017.7777 EP - 9644 IS - 6 JO - Mol Med Rep KW - isoimperatorin osteoarthritis hypertrophic chondrocyte angiogenesis autophagy mammalian target of rapamycin PY - 2017 SN - 1791-2997 1791-3004 SP - 9636 ST - Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway T2 - Molecular Medicine Reports TI - Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway UR - https://doi.org/10.3892/mmr.2017.7777 VL - 16 ER -