Braun Sebastian, Pollinger Patrizia, Sohn Rebecca, Rapp Anna E, Rösch Gundula, Zaucke Frank, Jenei-Lanzl Zsuzsa
Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Department of Trauma Surgery and Orthopedics, Goethe University Frankfurt, University Hospital, Marienburgstraße 2, D-60528, Frankfurt am Main, Germany.
Arthritis Res Ther. 2025 Aug 26;27(1):170. doi: 10.1186/s13075-025-03615-7.
During osteoarthritis (OA) pathogenesis, the infrapatellar fat pad (IFP) undergoes fibrotic changes that might contribute to pain development. Recent studies have demonstrated that thrombospondin-4 (TSP-4), first detected in the extracellular matrix of cartilage and released during its degradation, has been implicated in the pathogenesis of pain. Therefore, we analyzed TSP-4 levels in the IFP and synovial fluid and correlated this data with IFP fibrosis and knee joint pain.
IFP and synovial fluid were collected from patients undergoing total knee replacement surgery. Total WOMAC total and pain scores were determined preoperatively. IFP sections were stained using standard Masson trichrome and hematoxylin/eosin dyes to assess fibrotic changes, number of vessels and lymphocytic infiltration. TSP-4 expression in the IFP was detected immunohistochemically. TSP-4 in synovial fluid samples was quantified using ELISA.
TSP-4 was detectable in human IFP tissue at the protein level and its expression levels showed a positive correlation with the degree of tissue fibrosis. Regarding the degree of fibrosis and TSP-4-stained areas, four patient subgroups could be distinguished. Notably, moderate levels of TSP-4 expression were already detectable in samples exhibiting a low degree of fibrosis. There was no significant correlation between TSP-4 staining intensity in IFP and pain. There was no correlation between TSP-4 staining intensity and synovial fluid TSP-4 concentrations. A significant relationship between synovial fluid TSP-4 concentration and pain intensity was only found in female OA patients.
TSP-4 has been detected in the IFP for the first time. The correlation between TSP-4 expression and fibrotic severity indicates a possible involvement of TSP-4 in the development of fibrosis. Although TSP-4 within the IFP may not directly mediate pain, its presence in synovial fluid could be of functional relevance in pain-related mechanisms. Further analysis of synovial fluid and even serum samples from larger patient populations will determine whether TSP-4 could serve as a biomarker for pain or potentially represent a novel target for analgesic therapies.
在骨关节炎（OA）发病过程中，髌下脂肪垫（IFP）会发生纤维化改变，这可能促使疼痛加剧。最近的研究表明，血小板反应蛋白-4（TSP-4）最初在软骨细胞外基质中被检测到，并在软骨降解时释放，与疼痛的发病机制有关。因此，我们分析了IFP和滑液中TSP-4的水平，并将这些数据与IFP纤维化和膝关节疼痛进行关联。
从接受全膝关节置换手术的患者中收集IFP和滑液。术前测定WOMAC总分和疼痛评分。IFP切片采用标准的Masson三色染色法和苏木精/伊红染色法，以评估纤维化改变、血管数量和淋巴细胞浸润情况。采用免疫组织化学法检测IFP中TSP-4的表达。使用酶联免疫吸附测定法（ELISA）对滑液样本中的TSP-4进行定量分析。
在人IFP组织中可检测到蛋白质水平的TSP-4，其表达水平与组织纤维化程度呈正相关。根据纤维化程度和TSP-4染色区域，可将患者分为四个亚组。值得注意的是，在纤维化程度较低的样本中已可检测到中等水平的TSP-4表达。IFP中TSP-4染色强度与疼痛之间无显著相关性。TSP-4染色强度与滑液中TSP-4浓度之间无相关性。仅在女性OA患者中发现滑液TSP-4浓度与疼痛强度之间存在显著关系。
首次在IFP中检测到TSP-4。TSP-4表达与纤维化严重程度之间的相关性表明TSP-4可能参与了纤维化的发展过程。虽然IFP中的TSP-4可能不会直接介导疼痛，但其在滑液中的存在可能与疼痛相关机制具有功能相关性。对更多患者群体的滑液甚至血清样本进行进一步分析，将确定TSP-4是否可作为疼痛的生物标志物，或潜在地代表镇痛治疗的新靶点。
