Department of Joint Surgery, Tianjin Hospital, Tianjin Medical University, Tianjin 300211, P.R. China.
Mol Med Rep. 2018 Apr;17(4):5454-5462. doi: 10.3892/mmr.2018.8531. Epub 2018 Jan 31.
The present study investigated the role of microRNA (miR)‑27a in the development of arthritis and its mechanism of action. Initially, collagen was used to develop an in vivo rat model of arthritis. Changes in the miRs in the rats were analyzed. It was subsequently observed that miR‑27a expression was reduced in patients with arthritis, compared with the control group. In the present study an in vitro miR‑27a overexpression model of arthritis was established and it was observed that miR‑27a increased the proliferation of osteoblast‑like cells in vitro. miR‑27a overexpression promoted osteogenic differentiation, increased alkaline phosphatase (ALP) and osteoporosis (OST) content, induced insulin‑like growth factor binding protein-5 (IGFBP‑5) protein expression, reduced inflammation and suppressed peroxisome proliferator‑activated receptor γ (PPARγ) and matrix metalloproteinase-17 (MMP‑17) protein expression in arthritis. However, miR‑27a downregulation inhibited osteogenic differentiation, increased inflammation and PPARγ and MMP‑17 protein expression and suppressed ALP and OST content in an in vitro model of arthritis. The PPARγ inhibitor reduced the function of miR‑27a downregulation on arthritis. Therefore the results of the present study revealed that miR‑27a regulates arthritis via PPARγ.
本研究探讨了 microRNA（miR）-27a 在关节炎发展中的作用及其作用机制。首先，使用胶原蛋白建立关节炎大鼠体内模型。分析大鼠中 miR 的变化。随后观察到，与对照组相比，关节炎患者 miR-27a 的表达降低。本研究建立了关节炎 miR-27a 过表达的体外模型，观察到 miR-27a 增加了体外成骨样细胞的增殖。miR-27a 过表达促进成骨分化，增加碱性磷酸酶（ALP）和骨质疏松（OST）含量，诱导胰岛素样生长因子结合蛋白-5（IGFBP-5）蛋白表达，减少炎症，抑制过氧化物酶体增殖物激活受体γ（PPARγ）和基质金属蛋白酶-17（MMP-17）蛋白表达在关节炎中。然而，miR-27a 下调抑制成骨分化，增加炎症和 PPARγ 和 MMP-17 蛋白表达，并抑制 ALP 和 OST 含量在关节炎的体外模型中。PPARγ 抑制剂降低了 miR-27a 下调对关节炎的作用。因此，本研究结果表明，miR-27a 通过 PPARγ 调节关节炎。
