Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor, Catherine Cookson Building, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Bone and Joint Research Unit, Instituto de Investigación, Fundación Jiménez Díaz, Universidad Autónoma de Madrid (UAM), Avenida Reyes Católicos, Madrid, Spain.
Nat Rev Rheumatol. 2015 Mar;11(3):159-70. doi: 10.1038/nrrheum.2014.209. Epub 2014 Dec 16.
Osteoarthritis (OA), the most common rheumatic disease, is characterized by joint-space narrowing due to progressive cartilage degradation and alterations in subchondral bone and the synovial membrane. These articular disturbances can have severe consequences, including pain, disability and loss of joint architectural integrity. Although the aetiology of OA is not understood, chondrocyte-mediated inflammatory responses triggered by the activation of innate immune receptors by damage-associated molecules are thought to be involved. In this Review, we examine the relationship between Toll-like receptor 4 (TLR4) and OA in cartilage as well as in other OA-affected tissues, such as subchondral bone and synovium. We also discuss the different TLR4 agonists associated with OA and their effects in joint tissues. Finally, we describe existing and novel strategies that might be used to develop TLR4-specific disease-modifying OA drugs (DMOADs).
骨关节炎（OA）是最常见的风湿性疾病，其特征是由于软骨渐进性退化以及软骨下骨和滑膜的改变导致关节间隙变窄。这些关节紊乱可能会产生严重后果，包括疼痛、残疾和关节结构完整性丧失。尽管 OA 的病因尚不清楚，但人们认为，损伤相关分子激活固有免疫受体引发的软骨细胞介导的炎症反应与之相关。在这篇综述中，我们研究了 TLR4 与软骨以及其他 OA 相关组织（如软骨下骨和滑膜）中的 OA 之间的关系。我们还讨论了与 OA 相关的不同 TLR4 激动剂及其在关节组织中的作用。最后，我们描述了现有的和新的策略，这些策略可能用于开发 TLR4 特异性的治疗骨关节炎的药物（DMOADs）。
