Osteoarthritis (OA) is a chronic degenerative disease that mostly occurs in elderly individuals over 60 years old. The detailed pathogenesis of OA is unclear. Medicines available on the market are nonsteroidal anti-inflammatory drugs. Therefore, in this study, a fusion protein was introduced, and the detailed mechanism that could alleviate OA was discussed. As a targeted protein, HB-NC4 showed better binding ability to chondrocytes, and its half-life period was prolonged compared to NC4 alone. In addition, HB-NC4 can not only affect the levels of C3 and C5, but also inhibit the formation of the membrane-attack complex (MAC, C5b-9), thereby further affecting the expression of MAPK signalling pathway-related proteins to achieve the goal of treating OA. Thus, in this study, we demonstrate the pharmacokinetics of HB-NC4 and its mechanism to alleviate OA by regulating the complement system and MAPK signalling pathway. This study provides a new method for OA therapy based on fusion proteins.

骨关节炎（OA）是一种慢性退行性疾病，主要发生在 60 岁以上的老年人身上。OA 的详细发病机制尚不清楚。市场上出售的药物是非甾体抗炎药。因此，在本研究中，引入了一种融合蛋白，并讨论了缓解 OA 的详细机制。作为靶向蛋白，HB-NC4表现出更好的软骨细胞结合能力，与单独的NC4相比，其半衰期延长。此外，HB-NC4不仅可以影响C3和C5的水平，还可以抑制膜攻击复合物（MAC、C5b-9）的形成，从而进一步影响MAPK信号通路相关蛋白的表达，从而达到治疗 OA 的目标。因此，在本研究中，我们证明了 HB-NC4 的药代动力学及其通过调节补体系统和 MAPK 信号通路减轻 OA 的机制。本研究为基于融合蛋白的骨关节炎治疗提供了一种新方法。