Min Nan, Ma Jie, Shi Lei, Wang Lin, Liu Chi, Zhang Yaonan, Xue Qingyun
Department of Orthopedics, Beijing Hospital, Beijing, China.
Center of Biotherapy, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Arch Med Sci. 2020 Nov 6;20(6):2002-2008. doi: 10.5114/aoms.2020.100640. eCollection 2024.
The present investigation evaluates the role of miR-223 mimic in the treatment of osteoarthritis (OA) and postulates the possible molecular mechanism of its action.
Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from rats and cultured in chondrogenic medium to stimulate the differentiation of chondrocytes. Alcian blue staining was performed to determine the chondrogenic differentiation and expression of miR-223 in the BMSCs. Moreover, expression of NLR family pyrin domain containing 3 (NLRP-3), matrix metallopeptidase-13 (MMP-13) and collagen (Col II) was determined in miR-223 mimic and inhibitor treated BMSCs. OA was induced by injecting anterior cruciate ligament transection in rats followed by further treatment with the miR-223 mimic for the period of the treatment protocol. Level and expression of inflammatory cytokines were estimated in the cartilage tissue of OA rats. Moreover, immunohistochemical analysis and histopathology study were also performed.
Data of the study reveal that expression of miR-223 was higher in chondrogenic differentiated BMSCs than normal. Expression of MMP-13 and NLRP-3 was lower, and expression of Col II was higher in miR-223 mimic treated BMSCs than normal. Moreover, data of the study indicate that the expression level of cytokines was lower in the cartilage tissue of the miR-223 mimic treated group than the OA group. Treatment with the miR-223 mimic ameliorates the altered histopathology and expression of NLRP-3 in the cartilage tissue of OA rats.
Data of the study reveal that the miR-223 mimic enhances the chondrogenic differentiation of BMSCs by regulating the NLRP-3/IL-18/TGF-β pathway.
本研究评估了miR - 223模拟物在骨关节炎（OA）治疗中的作用，并推测其可能的分子作用机制。
从大鼠中分离出骨髓间充质干细胞（BMSCs），并在软骨生成培养基中培养以刺激软骨细胞分化。进行阿尔新蓝染色以确定BMSCs中软骨生成分化及miR - 223的表达。此外，还测定了经miR - 223模拟物和抑制剂处理的BMSCs中含NLR家族吡啉结构域3（NLRP - 3）、基质金属蛋白酶 - 13（MMP - 13）和胶原蛋白（Col II）的表达。通过在大鼠中注射前交叉韧带横断术诱导OA，随后在治疗方案期间用miR - 223模拟物进一步治疗。评估OA大鼠软骨组织中炎性细胞因子的水平和表达。此外，还进行了免疫组织化学分析和组织病理学研究。
研究数据显示，软骨生成分化的BMSCs中miR - 223的表达高于正常水平。与正常情况相比，经miR - 223模拟物处理的BMSCs中MMP - 13和NLRP - 3的表达较低，而Col II的表达较高。此外，研究数据表明，miR - 223模拟物处理组软骨组织中细胞因子的表达水平低于OA组。用miR - 223模拟物治疗可改善OA大鼠软骨组织中改变的组织病理学和NLRP - 3的表达。
研究数据表明，miR - 223模拟物通过调节NLRP - 3/IL - 18/TGF -β途径增强BMSCs的软骨生成分化。
