Institute of Biomechanics and Orthopaedics, German Sport University Cologne, 50933 Cologne, Germany.
Cologne Center of Musculoskeletal Biomechanics (CCMB), Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Int J Mol Sci. 2021 Mar 17;22(6):3073. doi: 10.3390/ijms22063073.
Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.
骨关节炎（OA）是一种多因素疾病，其特征在于细胞外基质（ECM）的动态平衡发生变化。ECM 对关节软骨的功能至关重要，并在软骨机械转导中发挥重要作用。为了更好地理解 ECM 与肌动蛋白细胞骨架之间的相互作用，我们研究了钙依赖性蛋白软骨寡聚基质蛋白（COMP）、血小板反应蛋白-1（TSP-1）、塑性 3（PLS3）和基质相互作用分子 1（STIM1）的定位和表达。我们研究了 16 名患有内翻膝 OA 的患者，并对胫骨近端平台内侧和外侧间室的软骨进行了拓扑分析。在内翻膝中，由于对线不良导致的过度负荷，OA 在内侧间室比外侧间室更为明显。我们在关节软骨组织中检测到 PLS3 和 STIM1 的位置依赖性染色。这两种蛋白质的染色强度与软骨退变程度相关。TSP-1 在受影响更严重的内侧间室软骨中的染色强度明显降低，这一观察结果通过免疫印迹在软骨提取物中得到了证实。COMP 的总量没有变化；然而，在蛋白的定位上检测到了细微的变化。我们的研究结果提供了 OA 软骨中改变的新信息，表明 ECM 和肌动蛋白细胞骨架之间的钙依赖性机械转导可能在 OA 的发病机制中发挥重要作用。
