PDF(Pubmed)
Abstract：
Osteoarthritis (OA) is a challenging degenerative joint disease to manage. Previous research has indicated that cell-free fat extract (CEFFE) may hold potential for OA treatment. This study investigated the role of Annexin A5 (AnxA5) within CEFFE in regulating macrophage polarization and protecting chondrocytes. In vitro experiments demonstrated that AnxA5 effectively inhibited M1 macrophage polarization by facilitating toll-like receptor (TLR) 4 internalization and lysosomal degradation through calcium-dependent endocytosis. This process decreased TLR4 expression, suppressed pro-inflammatory mediator release, and reduced the production of reactive oxygen species. Furthermore, AnxA5 displayed protective effects against chondrocyte necrosis and apoptosis. In vivo, studies revealed that intra-articular administration of AnxA5 ameliorated pain symptoms in a monosodium iodoacetate-induced osteoarthritis rat model. Histological analyses indicated a decrease in synovial inflammation and mitigation of cartilage damage following AnxA5 treatment. These results underscored the potential of AnxA5 as a therapeutic option for OA due to its capacity to regulate macrophage polarization and maintain chondrocyte viability. Further investigation into the specific mechanisms and clinical applications of AnxA5 may help improve the management of OA.
摘要：
骨关节炎（OA）是一种具有挑战性的退行性关节疾病。先前的研究表明，无细胞脂肪提取物（CEFFE）可能具有治疗OA的潜力。这项研究调查了CEFFE中膜联蛋白A5（AnxA5）在调节巨噬细胞极化和保护软骨细胞中的作用。体外实验表明，AnxA5通过促进Toll样受体（TLR）4内化和通过钙依赖性内吞作用的溶酶体降解，有效抑制M1巨噬细胞极化。这一进程下降了TLR4的表达，抑制促炎介质释放，并减少了活性氧的产生。此外，AnxA5对软骨细胞坏死和凋亡具有保护作用。在体内,研究表明，在碘乙酸钠诱导的骨关节炎大鼠模型中，关节内给予AnxA5改善了疼痛症状。组织学分析表明，AnxA5治疗后，滑膜炎症反应减少，软骨损伤减轻。这些结果强调了AnxA5由于其调节巨噬细胞极化和维持软骨细胞活力的能力而作为OA的治疗选择的潜力。进一步研究AnxA5的具体机制和临床应用可能有助于改善OA的管理。
