活体荧光示踪GFP/RfLuc-BMSC归巢重塑骨关节炎肾虚小鼠软骨细胞功能的机制研究

骨关节炎是一种常见、难治的退变性疾病，准确掌握其病因病机，有助于提高临床疗效与发挥中医优势。课题组初步揭示肾虚髓亏，骨髓生化乏源，则筋骨失充，而发骨关节炎，以软骨细胞功能失调介导软骨退变为病理特征。骨髓基质干细胞（BMSC）归巢重塑软骨细胞，是髓充骨的功能体现，为肾所主；但在活体状态BMSC归巢与骨关节炎肾虚的内在联系是亟待解决的科学问题。本研究以骨关节炎肾虚小鼠模型为研究对象：（1）活体荧光示踪GFP/RfLuc-BMSC归巢软骨的迁移与分化特点，活体荧光成像观察关节内MMP荧光探针的激活，探讨BMSC归巢重塑软骨细胞功能的活体评价方法；（2）采用补肾壮筋汤干预，检测GFP/RfLuc-BMSC归巢与软骨基质稳态的关键调控因子表达，从方证对应的角度揭示BMSC归巢重塑软骨细胞功能的调控靶点，旨在丰富肾虚的病因病机，进一步诠释肾生髓充骨的科学内涵，为骨关节炎中医诊疗的客观化研究提供新模式。

Osteoarthritis (OA) is a common and incurable degenerative disease. An accurate understanding of etiology and pathogenesis of OA contributes to improving clinical curative effect and exerting advantages of traditional Chinese medicine (TCM). Based on the former solid works, Kidney-Marrow Deficiency leads to bone marrow deficiency failing to nourish the tendon and bone, and then causes the formation of OA with the feature of chondrocyte dysfunction mediated cartilage degeneration. It's a functional reflection of marrow filling bone that bone marrow stromal stem cell (BMSC) homing remodeling of chondrocyte function is dominated by the kidney. However, it is a burning issues that the internal relations of BMSC homing and Kidney Deficiency in vivo. Therefore, a mouse model of OA Kidney Deficiency is established to do the following researches. (1) It is to found the evaluation method of BMSC homing remodeling chondrocyte function by observing migration and differentiation characteristics of GFP/RfLuc-BMSC homing cartilage and activation of MMP fluorescent probe using fluorescent tracing and imaging in vivo. (2) It is to reveal the targets of BMSC homing remodeling chondrocyte function by measuring key regulatory factor expressions of BMSC homing and cartilage matrix homeostasis after Bushen Zhuangjin Decoction administration from the view of corresponding formula and syndrome. These works are to enrich the etiology and pathogenesis of Kidney Deficiency and furtherly explore the scientific connotation of Kidney- Generating-Marrow-Nourishing-Bone to provide a new strategy for the study on objectivity of OA diagnosis and treatment of TCM.