骨关节炎骨赘形成的分子信号通路研究进展

The signaling pathways of osteophyte forming in osteoarthritis

骨关节炎(OA)是一种与年龄具有高度正相关性的退行性疾病。目前,OA尚无有效的临床治愈方案,以缓解症状为主。其主要原因在于对OA的分子发病机制尚未明了。根据分子信号通路网络的复杂性,在OA早期针对某一个信号通路进行干预,看似可以对OA软骨细胞某一个病变如分化终端肥大化进行治疗或预防,然而OA早期到晚期之间是否一定存在直线性进展,有待明确。肥胖、老年性退化、代谢性疾病、关节畸形或者外伤等疾病均可诱导OA,OA不能简单的被认为是一个独立的疾病。正常的软骨细胞在分化完成后会更注重维持内环境稳定,防止"两极变化",即分解性病变和肥大性病变,其中软骨细胞肥大性病变将诱导骨赘的形成。软骨内骨化是OA骨赘形成一个非常重要的过程。调控软骨内骨化过程的信号通路包括了Wnt/β-catenin、Ihh/PTHr P、TGF-β、MAPK、FGF、Notch、炎症及缺氧相关的信号通路。本文将对这些因素做一简要综述。

Osteoarthritis(OA),highly relating to age,is a degenerative disease.Currently,there is no effective cure for OA,but relieve the clinical symptoms.The main reasons responsible for it are the poor understanding of molecular mechanism of OA.Due to the net complexity of signaling pathways,interference with one signaling in the early stage of OA for a specific phenotype,such as hypertrophy,seems reasonable for prevention or management.However,whether there is a linear development from the early to the late stage of OA is still unclear.Clinically,many diseases,such as obesity,aging degeneration,metabolic diseases,joint deformity or trauma,can lead to OA.This makes OA not to be considered as an independent disease.After differentiation,normal chondrocytes function to sustain homeostasis,which is to prevent from''two-polar switch'':catabolic change or hypertrophic change.Chondrocytes hypertrophy leads to osteophyte formation.The pathological processes of endochondral ossification play a crucial role in osteophyte formation in OA.Regulation of endochondral ossification-related signaling pathways include Wnt/β-catenin,Ihh/PTHrP,TGF-β,MAPK,FGF,Notch,inflammatory and hypoxia signaling.This review will comprehensively discuss these signaling pathways.