CRLF1在股骨头坏死关节软骨退变的变化及其调控机制

The degeneration of articular cartilage is associated with osteonecrosis during the course of femoral head necrosis. The current treatment of hip surgery only focus on the reconstruction of necrotic bone in the femoral head, did not achieve satisfactory clinical results. In-depth understanding of cartilage degeneration in the process of necrosis of the femoral head and its regulatory mechanism, for the intervention of osteonecrosis in the process of cartilage degeneration and the development of scientific treatment of hip hip is of great significance. Our early gene expression profiles suggest that elevated expression of CRLF1 may be associated with aortic cartilage lesions. This study focused on the changes and regulatory mechanisms of the femoral head cartilage in the process of femoral head necrosis and collapse. The expression and function of CRFL1 were studied in depth to study the pathophysiologic changes of articular cartilage during the necrosis of the femoral head and its involvement in the pathological changes of cartilage Regulatory mechanism. (Collapse and post-collapse) and space (subsidence and non-subsidence areas) of the femoral head cartilage degeneration during the collapse of the femoral head and its regulation mechanism. The phenotypic reversibility of cartilage degeneration was observed by cartilage culture in vitro. Aiming at finding the target of intervention for cartilage degeneration during the process of femoral head necrosis, and providing scientific basis for designing more scientific hip treatment.

股骨头坏死病程中骨坏死与毗邻的软骨退变相伴而生。目前的保髋治疗方案仅着眼于股骨头内坏死骨质的重建，并未取得令人满意的临床效果。深入认识股骨头坏死过程中的软骨退变及其调控机制，对于干预骨坏死过程中的软骨退变及制定科学的保髋治疗方案具有重要的意义。我们前期的基因表达谱研究提示，CRLF1的表达增高可能和股骨头软骨病变密切相关。本研究着眼于股骨头坏死塌陷过程中股骨头软骨的变化及其调控机制，围绕CRFL1的表达及功能来深入研究股骨头坏死塌陷过程中关节软骨的特征性变化，及其参与软骨组织病理变化的调控机制。揭示坏死塌陷过程中股骨头软骨退变的时间（塌陷前和塌陷后）和空间（塌陷区和非塌陷区）变化及其调控机制。通过软骨片体外培养观察在软骨营养重新获得后软骨组织退变的表型可逆性变化。旨在为股骨头坏死过程中软骨退变寻找干预的靶点，为设计更为科学精准的保髋治疗方案提供科学依据。

股骨头坏死病程中骨坏死与毗邻的软骨退变相伴而生。目前的保髋治疗方案仅着眼于股骨头内坏死骨质的重建，并未取得令人满意的临床效果。深入认识股骨头坏死过程中的软骨退变的病理变化及其调控机制，对于干预骨坏死过程中的软骨退变及制定科学的保髋治疗方案具有重要的意义。本研究着眼于深入研究股骨头坏死软骨退变的病理变化，CRLF1在股骨头坏死塌陷期软骨的表达变化，以及CRLF1对软骨细胞基质合成的调控作用。发现股骨头坏死塌陷期软骨软骨厚度变薄，软骨基质减少，软骨细胞数减少，软骨细胞排列紊乱。CRLF1在股骨头坏死塌陷期软骨的表达增加，CRLF1过表达可以显著促进软骨细胞软骨基质Ⅱ型胶原和蛋白聚糖的合成。通过过表达CRLF1促进软骨细胞合成软骨细胞基质从而达到对软骨退变的修复，因此对该基因的干预有望成为股骨头坏死塌陷期保髋治疗过程中软骨退变修复的一个治疗干预靶点。另外，本研究对股骨头坏死塌陷期软骨进行全基因甲基化检测和蛋白质组学的检测，并进行深入的生物信息学分析及实验结果的验证，发现了与股骨头坏死软骨退变密切相关一些基因的超甲基化位点和去甲基化位点，以及软骨退变密切相关的差异表达的蛋白分子，这些的都为我们后续进一步深入研究股骨头坏死软骨退变提供了有益的线索和奠定了基础。