Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, and Division of Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, Sweden.
Osteoarthritis Cartilage. 2022 Sep;30(9):1198-1209. doi: 10.1016/j.joca.2022.06.009. Epub 2022 Jul 6.
To compare the concentrations of high mobility group box 1 protein (HMGB1) and S100A8/A9 in synovial fluid between patients with knee injuries and osteoarthritis (OA), and knee healthy subjects. To investigate associations of alarmin levels with different joint injuries and with biomarkers of inflammation, Wnt signaling, complement system, bone and cartilage degradation.
HMGB1 and S100A8/A9 were measured in synovial fluid by immunoassays in patients with knee injuries, with OA and from knee healthy subjects, and were related to time from injury and with biomarkers obtained from previous studies. Hierarchical cluster and enrichment analyses of biomarkers associated to HMGB1 and S100A8/A9 were performed.
The synovial fluid HMGB1 and S100A8/A9 concentrations were increased early after knee injury; S100A8/A9 levels were negatively associated to time after injury and was lower in the old compared to recent injury group, while HMGB1 was not associated to time after injury. The S100A8/A9 levels were also increased in OA. The initial inflammatory response was similar between the alarmins, and HMGB1 and S100A8/A9 shared 9 out of 20 enriched pathways. The alarmins displayed distinct response profiles, HMGB1 being associated to cartilage biomarkers while S100A8/A9 was associated to proinflammatory cytokines.
HMGB1 and S100A8/A9 are increased as an immediate response to knee trauma. While they share many features in inflammatory and immunoregulatory mechanisms, S100A8/A9 and HMGB1 are associated to different downstream responses, which may have impact on the OA progression after acute knee injuries.
比较膝关节损伤和骨关节炎（OA）患者与膝关节健康受试者关节滑液中高迁移率族蛋白 1（HMGB1）和 S100A8/A9 的浓度。探讨警报素水平与不同关节损伤以及与炎症、Wnt 信号、补体系统、骨和软骨降解的生物标志物的关系。
采用免疫分析法检测膝关节损伤、OA 患者及膝关节健康受试者关节滑液中 HMGB1 和 S100A8/A9 的浓度，并与损伤后时间及先前研究获得的生物标志物相关。对与 HMGB1 和 S100A8/A9 相关的生物标志物进行层次聚类和富集分析。
膝关节损伤后早期关节滑液 HMGB1 和 S100A8/A9 浓度升高；S100A8/A9 水平与损伤后时间呈负相关，且老年组低于近期损伤组，而 HMGB1 与损伤后时间无关。OA 患者 S100A8/A9 水平也升高。两种警报素的初始炎症反应相似，HMGB1 和 S100A8/A9 有 9 个富集途径重叠。警报素表现出不同的反应特征，HMGB1 与软骨生物标志物相关，而 S100A8/A9 与促炎细胞因子相关。
HMGB1 和 S100A8/A9 是膝关节创伤后即刻反应增加的结果。虽然它们在炎症和免疫调节机制中有许多共同特征，但 S100A8/A9 和 HMGB1 与不同的下游反应相关，这可能对急性膝关节损伤后 OA 的进展有影响。
