膝关节骨性关节炎中软骨下骨板的显微组织形态学变化及其与血管生成的关系

Knee osteoarthritis (OA) is the most prevalent type of OA, and a major cause of pain and disability in the aging population. Subchondral bone, consisting of subchondral bone plate (SBP) and subchondral trabecular bone (STB), has been reported to play a pivotal role in both the initiation and progression of knee OA. As a dense mineralized lamella lying between cartilage and deeper bone tissue, SBP acts as a biomechanical and biochemical shield for the underlying STB. Subchondral microvasculature is deeply involved in the osteoarthritic degeneration of the cartilage. However, the role of microvasculature in the deterioration of subchondral bone is poorly investigated. Consequently, we hypothesize that SBP damage may have a substantial correlation with the abnormal changes of STB and SBCs formation in knee OA; microvasculature is closely involved in the subchondral bone degeneration. To address this, we will recruit 200 patients with knee OA, and extract subchondral bone cylinders from the load-bearing region of tibial plateau after the knee replacement. Then we will investigate the influence of microstructural and microvascular alterations in SBP on the STB microarchitecture and remodeling activity, and SBCs frequency, by means of micro-CT and histomorphometry. Histopathological changes of SBCs and their influence on the surrounding trabecular bone will also be assessed. Following the clinic study, a knee OA animal model will be established by intra-articular injection of collagenase. A prospective study is designed to assess the alterations of SBP and STB in different phases of knee OA in the following aspects: microarchitecture, biomechanical characteristics, histological bone remodeling level, and microvasculature. The dynamic correlations between SBP integrity and STB homeostasis, SBCs formation will be evaluated. Finally, an in vitro experiment is designed to the characteristics of subchondral bone-derived endothelial cells and its influence on bone metabolism in OA.

膝关节骨性关节炎（OA）是导致老年人疼痛和残疾的主要原因。软骨下骨由软骨下骨板（SBP）和软骨下松质骨（STB）构成，在OA发生发展中发挥重要作用。而SBP特性对STB稳态影响的相关研究匮乏。在OA中，血管生成对软骨退变有重要影响，但微血管在软骨下骨退变中的作用却鲜有研究。据此我们提出假说：膝关节OA中，SBP损伤与STB稳态破坏密切相关；微循环异常可引起软骨下骨退变。为验证此假说，我们拟入组200例膝关节OA患者，获取其胫骨平台软骨下骨标本。通过micro-CT和组织形态学方法研究SBP微结构和微循环损伤对STB稳态、SBCs形成的影响，并评估SBCs的组织学类型及其对周围骨组织的作用。通过构建OA动物模型，研究在膝关节OA不同发展阶段，SBP和STB在显微结构、生物力学特性、组织学骨重建水平及微循环等方面的动态变化。最后通过体外实验评估OA中骨源性微血管内皮细胞特点及其对骨代谢影响。

骨性关节炎(OA)是导致老年人疼痛和残疾的主要原因。软骨下骨由软骨下骨板( SBP)和软骨下松质骨(STB)构成，在OA发生发展中发挥重要作用。而SBP特性对STB稳态影响的相关研究匮乏。在OA中，血管生成对软骨退变有重要影响，但微血管在软骨下骨退变中的作用却鲜有研究。据此我们提出假说:OA中，SBP损伤与STB稳态破坏密切相关;微循环异常可引起软骨下骨退变。为验证此假说，我们收集行关节置换的OA患者，获取其关节软骨下骨标本。通过micro-CT和组织形态学方法研究SBP微结构和微循环损伤对STB稳态、SBCs形成的影响，并评估SBCs的组织学类型及其对周围骨组织的作用。通过构建OA动物模型，研究在OA不同发展阶段，SBP和STB在显微结构、生物力学特性、组织学骨重建水平及微循环等方面的动态变化，以及微循环和骨代谢之间的相关性。

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