软骨与软骨下骨间信息交流在骨关节炎发病机制中起重要作用。研究表明WISP1是调控软骨和软骨下骨间TGFβ/Wnt关键信号通路，但机制尚不明确。我们前期工作发现异常应力下软骨和软骨下骨间信息交流异常是导致骨与软骨共同致病重要原因，同时同步辐射显微CT及磁共振可定量显示骨关节炎软骨成份、软骨细胞排列方式、胶原纤维形态及软骨下骨改变。本课题将制作稳定骨关节炎模型及利用WISP1基因敲除老鼠，通过磁共振/同步辐射显微CT/ 双光子显微镜等多模态影像及分子生物技术，探索：1）影像学定量评估在异常压应力下WISP1如何调节TGFβ/Wnt信号以影响膝关节骨关节炎软骨细胞和软骨下骨病变发生发展及微观结构 ；2）是否WISP1基因敲除老鼠中调控TGFβ/Wnt信号通路可以改变骨关节炎发生与发展。本研究将为WISP1作为骨关节炎靶向治疗靶点提供实验基础，为先进影像技术无创研究骨关节炎机制提供有效手段。

The biologic and/or mechanical crosstalk between cartilage and subchondral bone, being involved in the whole progression of osteoarthritis (OA), contributes to create a vicious circle in the degenerative process. The interaction between TGF beta and WNT pathways mediated by WISP-1 may play a critical role during OA progression at the bone-cartilage interface. The mechanism remains unclear. Our previous study demonstrated that the abnormal crosstalk in the bone-cartilage interface has been an important cause of the OA. Meanwhile, synchrotron radiation micro-CT（SR Micro-CT）and Magnetic Resonance Imaging (MRI) have the potential to reveal microstructure in human articular cartilage, including a true cellular resolution for human articular cartilage, the three-dimensional structure of collagen framework and quantitative study of bone and cartilage of the different stage of OA. In present study, we will use the SR Micro-CT and MRI, immunohistochemistry and cDNA microarray analysis technologies on anterior cruciate ligament transection (ACLT) osteoarthritis mouse models and WISP1-deficient mices, to explore: 1) Under the abnormal pressure, if the regulating of WISP1 and TGFβ/Wnt signal could influence the biologic and/or mechanical crosstalk between cartilage and subcondral bone, leading to the occurrence and development of OA. And furthermore the whole process could be evaluated by the quantitative imaging modality at the cellular level; 2) whether the regulation of TGFβ /Wnt signaling in WISP1-deficient mices could change the occurrence and development of osteoarthritis. Our study will not only provide a new avenue to understand the WISP1 as an emerging candidate for the targeted therapy, but also provide a noninvasive imaging assessment method for OA.