Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, Pakistan.
J Cell Mol Med. 2018 Nov;22(11):5753-5758. doi: 10.1111/jcmm.13826. Epub 2018 Aug 22.
The interplay between anabolic and catabolic factors regulates cartilage matrix homoeostasis. In OA, this balance is disrupted which results in cartilage degradation involving a plethora of inflammatory factors. Here, we identify a novel gene "Scm-like with four MBT domains protein 2" (SFMBT2) negatively regulated in OA cartilage. Articular cartilage from human OA patients undergoing knee arthroplasty surgery exhibited significantly decreased levels of SFMBT2 compared to the normal controls. Down-regulation of SFMBT2 by specific siRNA disturbed the metabolic homoeostasis and led to decreased expression of anabolic genes (SOX9, COL2A1) while increasing the expression of catabolic genes (MMP13 and ADAMTS4), in human chondrocytes. Finally, we revealed that SFMBT2 intervention by siRNA contributed to the catabolic phenotype of human chondrocytes mediated by NF-kB pathway.
合成代谢和分解代谢因子之间的相互作用调节软骨基质的动态平衡。在 OA 中，这种平衡被打破，导致涉及大量炎症因子的软骨降解。在这里，我们确定了一种新的基因“具有四个 MBT 结构域的 Scm 样蛋白 2”（SFMBT2），其在 OA 软骨中受到负调控。与正常对照组相比，接受膝关节置换手术的人类 OA 患者的关节软骨中 SFMBT2 的水平显著降低。特异性 siRNA 下调 SFMBT2 扰乱了代谢平衡，导致合成代谢基因（SOX9、COL2A1）的表达减少，而分解代谢基因（MMP13 和 ADAMTS4）的表达增加，在人软骨细胞中。最后，我们揭示了 siRNA 对 SFMBT2 的干预通过 NF-kB 通路介导了人软骨细胞的分解代谢表型。
