炎性因子及信号通路在膝骨关节炎中的研究进展

Research progress of inflammatory factors and signaling pathways in knee osteoarthritis

膝骨关节炎(knee osteoarthritis,KOA)是骨伤科的常见病、多发病,已成为医学界的热点和难点。随着KOA研究的不断深入,炎性因子及相关信号通路在KOA发病机制中的作用逐渐被认识,已成为探索KOA发病机制的突破口。本文从炎症及相关信号通路的角度对KOA病理机制进行综述,发现与KOA相关的致炎因子主要有白介素-1β(interleukin-1β,IL-1β)、白介素-6(interleukin-6,IL-6)、白介素-17(interleukin-17,IL-17)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α);抗炎因子主要为转化生长因子-β(transforming growth factor-β,TGF-β)和白介素-10(interleukin-10,IL-10)。与炎性反应关系密切并和KOA病理过程相关的信号通路,主要有NF-κB信号通路、JAK/STAT信号通路及Wnt信号通路。这些致炎因子通过激活相关信号通路,促进炎性反应的发生,炎性反应又加重骨及软骨的退变,最终导致KOA的发生并进一步加重。而抗炎因子通过拮抗致炎因子,降低炎性反应,维持软骨细胞功能及细胞外基质的完整性,减轻骨及软骨的退变,从而缓解KOA临床症状。因此本文整理、归纳近年来与KOA相关的炎性因子及信号通路,以期在此基础上再融合miRNA对靶基因的调控,形成miRNA/信号通路/炎性因子调控轴,通过该调控轴精准调控炎性因子与信号通路,进而治疗KOA,将是中医药研究的有力方向,值得深入探索与挖掘。

Knee osteoarthritis(KOA)is a common and frequently occurring disease in orthopedics and traumatology,which is a challenging disease.With the deepening of KOA research,the role of inflammatory factors and relevant signaling pathways in the pathogenesis of KOA has been gradually recognized,serving as a breakthrough to explore the pathogenesis of KOA.This review aims to summarize the pathological mechanism of KOA from the perspective of inflammation and related signaling pathways.It is found that the main inflammatory factors related to KOA included interleukin-1β(IL-1β),IL-6,IL-17 and tumor necrosis factor-α(TNF-α).The main anti-inflammatory factors included transforming growth factor-β(TGF-β)and IL-10.The nuclear factor-kappa B(NF-kappa B),Janus Kinase/Signal Transducers and Activators of Transcription(JAK/STAT)and Wnt signaling pathways were inflammatory signals associated with KOA.These inflammatory factors promote the occurrence of inflammatory response by activating relevant signaling pathways,which aggravate the degeneration of bone and cartilage,and finally lead to the occurrence and further aggravation of KOA.Anti-inflammatory factors can reduce the inflammatory response,maintain the function of chondrocytes and the integrity of extracellular matrix,reduce the degeneration of bone and cartilage,and alleviate the clinical symptoms of KOA.Through summarizing inflammatory factors and relevant signaling pathways associated with KOA,and further exploration of the role of miRNAs in mediating KOA,a miRNA/inflammation signaling pathways/inflammatory factors axis is created to be a promising therapeutic strategy for KOA,especially in the research of traditional Chinese medicine.