Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopaedic University Hospital Friedrichsheim gGmbH, Marienburgstraße 2, 60528 Frankfurt/Main, Germany.
Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopaedics, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
Int J Mol Sci. 2019 Jan 21;20(2):447. doi: 10.3390/ijms20020447.
Osteoarthritis (OA) is a progressive joint disease characterized by a continuous degradation of the cartilage extracellular matrix (ECM). The expression of the extracellular glycoprotein thrombospondin-4 (TSP-4) is known to be increased in injured tissues and involved in matrix remodeling, but its role in articular cartilage and, in particular, in OA remains elusive. In the present study, we analyzed the expression and localization of TSP-4 in healthy and OA knee cartilage by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and immunoblot. We found that TSP-4 protein expression is increased in OA and that expression levels correlate with OA severity. TSP-4 was not regulated at the transcriptional level but we detected changes in the anchorage of TSP-4 in the altered ECM using sequential protein extraction. We were also able to detect pentameric and fragmented TSP-4 in the serum of both healthy controls and OA patients. Here, the total protein amount was not significantly different but we identified specific degradation products that were more abundant in sera of OA patients. Future studies will reveal if these fragments have the potential to serve as OA-specific biomarkers.
骨关节炎（OA）是一种渐进性关节疾病，其特征是细胞外基质（ECM）的持续降解。已知细胞外糖蛋白血小板反应蛋白-4（TSP-4）的表达在受伤组织中增加，并参与基质重塑，但它在关节软骨中的作用，特别是在 OA 中的作用仍不清楚。在本研究中，我们通过逆转录聚合酶链反应（RT-PCR）、免疫组织化学和免疫印迹分析了 TSP-4 在健康和 OA 膝关节软骨中的表达和定位。我们发现 TSP-4 蛋白表达在 OA 中增加，并且表达水平与 OA 的严重程度相关。TSP-4 不是在转录水平上调节的，但我们使用连续蛋白质提取检测到 TSP-4 在改变的 ECM 中的锚定变化。我们还能够在健康对照组和 OA 患者的血清中检测到五聚体和片段化的 TSP-4。在这里，总蛋白量没有显著差异，但我们鉴定出在 OA 患者血清中更丰富的特定降解产物。未来的研究将揭示这些片段是否有可能作为 OA 特异性生物标志物。
