Proteinases are enzymes with established roles in physiological and pathological processes such as digestion and the homeostasis, destruction and repair of tissues. Over the past few years, the hormone-like properties of circulating proteinases have become increasingly appreciated. Some proteolytic enzymes trigger cell signalling via proteinase-activated receptors, a family of G protein-coupled receptors that have been implicated in inflammation and pain in inflammatory arthritis. Proteinases can also regulate ion flux owing to the cross-sensitization of transient receptor potential cation channel subfamily V members 1 and 4, which are associated with mechanosensing and pain. In this Review, the idea that proteinases have the potential to orchestrate inflammatory signals by interacting with receptors on cells within the synovial microenvironment of an inflamed joint is revisited in three arthritic diseases: osteoarthritis, spondyloarthritis and rheumatoid arthritis. Unanswered questions are highlighted and the therapeutic potential of modulating this proteinase–receptor axis for the management of disease in patients with these types of arthritis is also discussed.

蛋白酶是在生理和病理过程中具有确定作用的酶，例如消化和体内稳态，组织的破坏和修复。在过去的几年中，循环蛋白酶的类激素性质已变得越来越受到重视。一些蛋白水解酶通过蛋白酶激活的受体触发细胞信号传导，该受体是G蛋白偶联受体的一个家族，已与炎症性关节炎的炎症和疼痛有关。由于瞬时受体电位阳离子通道亚家族V成员1和4的交叉敏化，蛋白酶还可以调节离子通量，这与机械感觉和疼痛有关。在这篇评论中，蛋白酶有可能通过与发炎关节的滑膜微环境内的细胞上的受体相互作用来协调发炎信号的想法在三种关节炎疾病中得到了重新探讨：骨关节炎，脊椎关节炎和类风湿性关节炎。突出了未解决的问题，并且还讨论了调节这种蛋白酶-受体轴对这些类型的关节炎患者的疾病治疗的治疗潜力。