期刊
JOURNAL OF INFLAMMATION RESEARCH
卷 14, 期 -, 页码 2317-2331出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/JIR.S312139
关键词
curcumin; osteoarthritis; apoptosis; autophagy; microRNA-34a; high-fat diet
类别
资金
- Key R&D Program of Liaoning Province [2020JH2/10300144]
- Natural Science Foundation of Liaoning Province [2019JH3/10300415]
Curcumin exerts chondroprotective effect by modulating miR-34a, upregulating E2F1/PITX1, and activating the Akt/mTOR pathway, reducing apoptosis and enhancing autophagy in osteoarthritis.
Purpose: The mechanism underlying curcumin's protective effect on osteoarthritis (OA) has not been clarified. This study aimed to determine whether curcumin exerts a chondroprotective effect by inhibiting apoptosis via upregulation of E2F1/PITX1 and activation of autophagy via the Akt/mTOR pathway by targeting microRNA-34a (miR-34a). Methods: Male Sprague-Dawley rats were fed a normal diet (ND) or high-fat diet (HFD) for 28 weeks. Five rats from each diet group were selected randomly for histological analysis of OA characteristics. Rats fed a HFD were given a single intra-stifle joint injection of the miR-34a mimic agomir-34a or negative control agomir (NC), followed by weekly low-dose (200 mu g/kg body weight) or high-dose (400 mu g/kg body weight) curcumin intra-joint injections from weeks 29 to 32. The rats' stifle joints were submitted to histological analysis and to an apoptotic assay. Expression of miR-34a was detected using a real-time RT-PCR. E2F1 and PITX1 protein levels were determined by Western blot analysis, and the expressions of Beelinl, LC3B, p62, phosphorylated (p)-Akt, and p-mTOR were measured using immunofluorescence analysis. Results: We found that rats fed a HFD had OA-like lesions in their articular cartilage and had increased apoptosis of chondrocytes and decreased autophagy compared to rats fed a ND. Curcumin treatment alleviated OA changes, inhibited apoptosis, and upregulated autophagy. Agomir-34a treatment reduced E2F1, PITX1, Beclin1, and LC3B expression and increased p62, p-Akt, and p-mTOR expression in HFD-fed rats given low- or high-dose curcumin. Greater numbers of apoptotic cells, lesser expression of p62, p-Akt, and p-mTOR, and greater expression of E2F1, PITX1, and LC3B were observed in the agomir-34a and high-dose curcumin-treated group than in agomir-34a and low-dose curcumin-treated group. Conclusion: Curcumin's chondroprotective effect was mediated by its suppression of miR-34a, apparently by reducing apoptosis, via upregulation of E2F1/PITX1, and by augmenting autophagy, likely via the Akt/mTOR pathway.
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