ALK1/ALK5失衡在颞下颌关节骨关节炎中的作用和机制研究

Temporomandibular joint osteoarthritis (TMJOA) is a common and frequently-occurring disease of the oral and maxillofacial surgery. Its pathogenesis of molecular mechanism is complex with poor treatment prognosis. This project tries to study its molecular mechanisms, clarify ALK1/ALK5 ratio imbalance possible as main risk factor and cause of the occurrence and development of TMJOA, and investigate the role of ALK1/ALK5 signal pathway ratio for TMJOA stem cell therapy with mesenchymal stem cells (MSCs). The main aims of this project include: 1) to investigate the effects of ALK1/ALK5 expression imbalance on proliferation, differentiation, apoptosis, and phenotypic changes, cartilage matrix secretion, and various types of TMJOA cytokines (such as type II collagen, and Smads, β-catenin, and MMP13 in primary cultured articular chondrocytes in vitro, 2) to establish TMJOA rabbit model for observation of spatial-temporal expression pattern of ALK1/ALK5, Smad2 / 3 signaling pathway molecules as well as other molecules related with the differentiation, proliferation and apoptosis of articular chondrocytes in normal articular cartilage and TMJOA to provide the experimental basis for TMJOA targeted therapy, 3) to study the effects of stem cell therapy for TMJOA with mesenchymal stem cells (MSCs) in which ALK1/ALK5 signal pathway is up-regulated or down-regulated. The launching of this project will contribute to elucidating the role of the TMJOA the pathogenesis and the regulation of Smads pathway, and thus provide the experimental basis for targeted therapy TMJOA. This project will elucidate molecular mechanisms of pathogenesis of TMJOA and regulation roles of ALK1/ALK5 and Smad2/3 signaling pathway and provide scientific basis for TMJOA targeted therapy.

颞下颌关节骨关节炎（Temporomandibular joint osteoarthritis,TMJOA）是口腔颌面外科的一种常见病和多发病，其发病机制复杂，治疗效果不理想。本项目拟研究其发病的分子生物学机制，阐明ALK1/ALK5信号通路的比例失衡可能是TMJOA发生和发展的重要原因。主要研究内容包括：1. 通过体外实验，观察ALK1/ALK5失衡与各类TMJOA相关信号分子表达的相互关系；研究ALK1/ALK5失衡在体外对软骨细胞分化的影响。2.建立实验动物模型，研究OA发生发展过程中ALK1/ALK5的时空表达变化规律。3.在TMJOA实验动物模型中，研究调控ALK1/ALK5比例关系对TMJOA的治疗效果。本项目的开展将有助于深入阐明ALK1/ALK5失衡对TMJOA的发生发展的调控作用，从而为靶向治疗TMJOA提供实验依据。

颞下颌关节骨关节炎（Temporomandibular joint osteoarthritis,TMJOA）是口腔颌面外科的一种常见病和多发病，其发病的细胞及分子生物学机制仍不清楚。本项目首次从ALK1/ALK5比例失调角度探讨细胞间信号传导在TMJOA发生、发展中的分子生物学机制。主要研究内容包括：1. 通过体外实验，观察ALK1/ALK5失衡与各类TMJOA相关信号分子表达的相互关系；研究ALK1/ALK5失衡在体外对MSCs向软骨细胞分化的影响。2.建立实验动物模型，研究OA发生发展过程中ALK1/ALK5的时空表达变化规律。3.在TMJOA实验动物模型中，研究调控ALK1/ALK5比例关系对TMJOA的治疗效果。本项目的开展将有助于深入阐明ALK1/ALK5失衡对TMJOA的发生发展的调控作用，从而为靶向治疗TMJOA提供实验依据。