赖氨酰氧化酶LOX在力学失稳性骨关节炎中的调控作用及相关分子机制

Osteoarthritis (OA) is a common soft tissue degenerative disease of the bone and joint system with high prevalence and disability. Although, previous studies have indicated that mechanical instability may be the key initiating factor in the occurrence of OA lesions, and found that inflammation is the key trigger in the occurrence of OA lesions. However, the specific mechanism of mechanical instability OA lesions is still unclear, and it is difficult to propose an effective therapeutic schedule. Our previous study detected that Lysyl oxidase (LOX) expression in cartilage with mechanical injury was significantly reduced and was considered to be an important factor in triggering mechanical instability OA lesions. Further experiments indicated that exogenous supplementation of LOX can protect chondrocytes withstanding extracellular matrix loss caused by severe inflammation, but the specific mechanism is unknown. Thus, this project will investigate the regulative effect of LOX in mechanical instability OA lesions; clarify the specific molecular mechanisms and targets of exogenous LOX for regulation of chondrocyte inflammation. Simultaneously, the role of exogenous LOX in the prevention and treatment of OA lesions was verified by the in vivo OA model. This study not only provides a new research idea for elucidating the mechanical instability degeneration mechanism of cartilage tissue, but also provides a potential feasible approach for OA treatment.

骨性关节炎 (osteoarthritis, OA) 是一种高患病率和致残率的退行性疾病。已有研究指出，力学失稳可能是OA病变发生的关键始动因素，炎症是OA病变发生的关键始动环节。然而，力学失稳引发的OA病变的具体机制及有效的治疗方案仍不明确。我们前期研究发现，力学损伤下调软骨赖氨酰氧化酶 (Lysyl oxidase, LOX) 的表达，并被认为是引发力学失稳性OA病变以及修复低效的重要因素。进一步实验发现，外源性补充LOX能够保护软骨细胞免于炎症引起的胞外基质丢失，但具体机理未知。因此，本项目将考察LOX在力学失稳性OA病变中的调控作用；并阐明外源性LOX调控软骨细胞炎症的具体分子机制和作用靶点。同时以在体OA模型为研究对象，验证外源性LOX防治OA病变的作用。本研究不仅能为阐明软骨组织的力学失稳性退变机制提供新的研究思路，还将为OA治疗提供一条潜在的可行性途径。

骨关节炎(Osteoarthritis, OA)是一种高患病率和致残率的退行性疾病。已有研究指出，力学失稳可能是OA病变发生的关键始动因素，炎症是OA病变发生的关键始动环节。然而，力学失稳引发的OA病变的具体机制及有效的治疗方案仍不明确。我们前期研究发现，力学损伤下调软骨赖氨酰氧化酶 (Lysyl oxidase, LOX) 的表达，并被认为是引发力学失稳性OA病变以及修复低效的重要因素。因此，本项目建立了力学失稳损伤的动物模型和细胞力学加载模型，从胞外基质结构稳定调节器（LOX）入手，探讨了LOX在软骨组织力学失稳损伤及修复中的调控作用及机制，提出了其对抗OA病变的技术与思路；并阐明外源LOX加入延缓力学失稳性OA病变的功能作用及LOX调控关节软骨损伤修复的力学生物学机制；设计、构建负载LOX的纳米水凝胶，开展材料表征和生物相容性检测以及开展体内、体外修复损伤软骨组织的作用研究，并揭示其修复机理。本研究不仅能为阐明软骨组织的力学失稳性退变机制提供新的研究思路，还将为OA治疗提供一条潜在的可行性途径。