波形蛋白破损对软骨细胞力学生物学的影响及其与骨关节炎发生的关系

Osteoarthritis is a common degenerative joint disease among aged people, its complex pathological mechanism has long been a concern in medical science.It is generally accepted that abnormal mechanical stimulus is one of the main factors that induce osteoarthritis.Therefore,as the only cell type in articular cartilage,the cytoskeletal mechanical properties of chondrocyte have become the research focus.Recent studies demonstrate that both progression of OA and large mechanical compression could significantly affect the expression and distribution of vimentin intermediate filaments in chondrocyte skeleton， but the function of vimentin in chondrocyte remains unclear. From the perspective of biomechanics,this research project focuses on the effects of vimentin disruption on mechanobiology of both normal and osteoarthritic chondrocytes. We will combine advanced cell mechanics approaches with conventional cell and molecular biology methods to measure the cytoskeleton viscoelasticity of chondrocytes under normal or pathlogical conditions, and observe the cell responses to large compressive strain. Then,we will compare the experimental results after vimentin disruption,and explain the correlation between the changes of biomechanical behaviors, metabolism, and phenotype of chondrocyte.By studying the role of vimentin in maitaining the mechanical and the biological properties of chondrocyte, we will reveal the correlation between biomechanical regulation mechanism of chondrocyte and pathological phenomena of osteoarthritis,and provide scientific foundation for exploring effective biophysical treatments of osteoarthritis.

骨关节炎是中老年人群中常见的关节退行性病变，其复杂的病理机制一直是医学科学的难题。异常应力刺激是公认的诱发骨关节炎的主要因素之一。因此，作为关节软骨内唯一的细胞种类，软骨细胞骨架的力学特性成为研究重点。近期研究表明，骨关节炎的发生发展和高压缩应力都能显著影响软骨细胞骨架中波形蛋白中间纤丝的表达和分布，但波形蛋白本身的作用不清。本项目拟从生物力学的角度，深入研究波形蛋白破损对正常和骨关节炎软骨细胞力学生物学的影响。将先进的细胞生物力学研究手段与传统的细胞和分子生物学方法结合，观测波形蛋白被破坏前后软骨细胞在正常和病理状态下的细胞骨架粘弹性和对高压缩应变的响应的变化，并解释软骨细胞的生物力学行为变化与软骨细胞的代谢，表型改变的关联。通过研究波形蛋白在维持软骨细胞力学特性和生物学特性上的作用，揭示软骨细胞生物力学调控机制与骨关节炎病理现象的关系，为探索有效诊治骨关节炎的生物物理方法提供科学基础。

软骨细胞作为关节软骨内的唯一细胞，在维持软骨的结构和功能上起了重要的作用。而关节力学微环境能能够显著影响软骨细胞的生物学功能。围绕软骨细胞力生物学这个主线，本项目组具体研究了生理病理条件下软骨细胞力学属性(Chen et al, Am J Physiol Cell Physiol 2013)，炎性因子对软骨细胞力生物学的作用(Chen et al, Acta Biochim Biophys Sin 2015)，细胞外基质刚度对软骨细胞力生物学的作用(Chen et al, ACS Appl Mater Interfaces 2014)，以及软骨细胞牵引力随力学、生物学刺激的变化(Chen et al, Biochem Biophys Res Commun 2016)等。