Liu Ziyu, Huang Yue, Jin Xin, Liu Li, Gu Hailun
Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, 110122, China.
Department of Orthopedics, Shengjing Hospital, China Medical University, 110004, China.
Toxicol Appl Pharmacol. 2022 Aug 15;449:116135. doi: 10.1016/j.taap.2022.116135. Epub 2022 Jun 19.
Polychlorinated biphenyls (PCBs) are a typical type of persistent organic pollutant. PCB exposure is associated to the occurrence and development of osteoarthritis (OA); however, the involved mechanisms have yet to be elucidated. Here, we investigated the pro-osteoarthritic effect of 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (PCB153), and the involvement of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) and the RICTOR/Akt/mTOR signaling pathways. PCB153 of 20 and 30 μM increased the expression of MMP13 and decreased the expression of type II collagen, in a concentration-dependent manner. PCB153 treatment reduced the expression of Beclin 1 and LC3B, but increased the expression of p62 by upregulating miR-155 levels. PCB153 treatment activated the PI3K/Akt/mTOR signaling pathway by upregulating miR-155 levels. RICTOR was involved in activating the Akt/mTOR signaling pathway, and was also regulated by miR-155. In conclusion, PCB153 could promote the degradation of the extracellular matrix of chondrocytes by upregulating miR-155 via a mechanism related to the activation of the PI3K/Akt/mTOR and RICTOR/Akt/mTOR signaling pathway, which suppressed autophagy and facilitated the development of OA. MiR-155 may represent potential therapeutic targets to alleviate the development of OA.
多氯联苯（PCBs）是一种典型的持久性有机污染物。接触PCBs与骨关节炎（OA）的发生和发展有关；然而，其涉及的机制尚未阐明。在此，我们研究了2, 2', 4, 4', 5, 5'-六氯联苯（PCB153）的促骨关节炎作用，以及磷酸肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/雷帕霉素哺乳动物靶蛋白（mTOR）和RICTOR/Akt/mTOR信号通路的参与情况。20和30μM的PCB153以浓度依赖的方式增加了MMP13的表达并降低了II型胶原蛋白的表达。PCB153处理降低了Beclin 1和LC3B的表达，但通过上调miR-155水平增加了p62的表达。PCB153处理通过上调miR-155水平激活了PI3K/Akt/mTOR信号通路。RICTOR参与激活Akt/mTOR信号通路，并且也受miR-155调控。总之，PCB153可通过与激活PI3K/Akt/mTOR和RICTOR/Akt/mTOR信号通路相关的机制上调miR-155，从而促进软骨细胞外基质的降解，抑制自噬并促进OA的发展。MiR-155可能是减轻OA发展的潜在治疗靶点。
