介孔硅纳米颗粒负载HAS2对颞下颌关节骨关节炎的治疗作用及机制研究

Osteoarthritis (OA) of temporomandibular joint (TMJ) is a degenerative disease featured by articular cartilage destruction accompanied with subchondral bone reconstruction and synovium inflammation. Hyaluronic acid (HA) injection is widely used in the treatment of TMJ OA. However, exogenous HA is quickly degraded by hyaluronidase once it is injected into the joint space, and inflammation would accelerate the degradation, which declined therapeutic effect of HA. In this project, we will establish mesoporous silica nanoparticles (MSN) co-delivery system combined with HAS2, and deliver it into synoval cells and TMJ disk cells of OA. Combined with transwell system, analysis of the concentration and molecular weight of HA will be performed by q-PCR and Western blotting. Meanwhile, we will explore the mechanism that how MSN-HAS2 increase the production of high molecular weight HA, and that how MSN-HAS2 affect the expression of inflammatory cytokines. Finally, MSN-HAS2 combined with/or IL-1β will be injected in the joint space of rat TMJ OA model in order to explore the curative effects in treating OA, providing a new method and idea for clinical treatment of OA.

颞下颌关节(TMJ)骨关节炎(OA)是一种发生在TMJ中以关节软骨破坏为主要特征，伴软骨下骨组织改建和滑膜炎症的退行性疾病。关节腔注射高分子量透明质酸（HA）已广泛应用于治疗OA，但注射后的外源性HA很快会被透明质酸酶降解，炎症的存在也会加速其降解，影响HA的治疗效果。本项目将构建透明质酸合成酶2(HAS2)与新型介孔硅（MSN）材料负载体系，将该体系转入OA滑膜细胞和关节盘细胞中，并结合transwell共培养系统，分析不同培养环境下该体系对HA分泌的影响，包括HA的浓度、分子量以及其促进高分子量HA合成的机制，并研究该体系对炎症相关因子表达的影响。最后通过大鼠OA模型结合MSN-HAS2负载体系关节腔内注射，研究其治疗TMJ OA的效果，为临床治疗提供新的方法和思路。

颞下颌关节(TMJ)骨关节炎(OA)是一种发生在TMJ中以关节软骨破坏为主要特征，伴软骨下骨组织改建和滑膜炎症的退行性疾病。关节腔注射高分子量透明质酸(HA)已广泛应用于治疗 OA，但注射后的外源性HA很快会被透明质酸酶降解，炎症的存在也会加速其降解，影响HA的治疗效果。本课题研究表明，生物可降解的介孔硅纳米颗粒能成功将透明质酸合成酶2(HAS2)，转入到滑膜细胞，并产生内源性高分子量HA。在大鼠TMJ骨关节炎炎症模型中，该负载体系能促进内源性HA的产生，并通过一次性给药抑制OA滑膜炎症3周以上，同时也有助于修复大鼠OA骨缺损模型的骨缺损。与现有HA注射方法持续时间短、需要多次注射不同，基于纳米颗粒的HAS2给药途径为OA的治疗提供了一种方便、高效的途径。