The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130000, People's Republic of China.
Department of Regeneration Medicine, School of Pharmaceutical Science of Jilin University, Changchun 130000, People's Republic of China.
Biosci Rep. 2018 Jan 10;38(1). doi: 10.1042/BSR20171109. Print 2018 Feb 28.
MicroRNAs (miRNAs) play an essential role in articular cartilage development and growth. However, the exact mechanisms involved in this process remain unknown. In the present study, we investigated the biological functions of during hypertrophic differentiation of rat articular chondrocytes. Based on hybridization and immunohistochemistry, we report that expression is reduced in the hypertrophic zone of articular cartilage, but expression of peroxisome proliferator-activated receptor γ (Pparγ) is increased. Dual-luciferase reporter gene assay and Western blot analysis demonstrated that Pparγ2 is a target of Overexpression of inhibited expression of Pparγ2, as well as type X collagen (Col10a1) and matrix metalloproteinase 13 (Mmp13), while significantly promoting the expression of Sex-determining Region-box 9 (Sox9) and type II collagen (Col2a1) at both the mRNA and protein levels. Rosiglitazone, a Pparγ agonist, suppressed Col2a1 expression, while promoting expression of runt-related transcription factor 2 (Runx2) and Col10a1 in a concentration-dependent manner. siRNA-mediated knockdown of Pparγ2 caused an increase in protein levels of Col2a1. The present study demonstrates that regulates chondrocyte hypertrophy in part by targetting Pparγ2, and that may have important therapeutic implications in cartilage diseases.
微小 RNA(miRNAs)在关节软骨的发育和生长中发挥着重要作用。然而,这一过程的确切机制仍不清楚。在本研究中,我们研究了在大鼠关节软骨细胞肥大分化过程中 的生物学功能。基于 杂交和免疫组织化学,我们报告说 在关节软骨的肥大区表达减少,而过氧化物酶体增殖物激活受体 γ(Pparγ)的表达增加。双荧光素酶报告基因检测和 Western blot 分析表明,Pparγ2 是 的靶基因。过表达 抑制 Pparγ2 的表达,以及型 X 胶原(Col10a1)和基质金属蛋白酶 13(Mmp13),同时显著促进 Sex 决定区框 9(Sox9)和型 II 胶原(Col2a1)的表达,在 mRNA 和蛋白质水平上均如此。Pparγ 激动剂罗格列酮以浓度依赖的方式抑制 Col2a1 的表达,同时促进 runt 相关转录因子 2(Runx2)和 Col10a1 的表达。Pparγ2 的 siRNA 介导的敲低导致 Col2a1 蛋白水平增加。本研究表明, 通过靶向 Pparγ2, 调节软骨细胞肥大,并且在软骨疾病中具有重要的治疗意义。