He Hua, Dong Dali
Department of Nursing, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410005, Hunan, China.
Department of Orthopedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410005, Hunan, China.
Regen Ther. 2025 Mar 12;29:77-90. doi: 10.1016/j.reth.2025.02.010. eCollection 2025 Jun.
The aim of this study was to investigate the regulation of Salvianolic acid A (SAA) on the chondrogenic differentiation of bone mesenchymal stem cells (BMSCs), and its effect on cartilage repair in knee osteoarthritis (KOA) model rats and the action mechanism.
Immunohistochemistry was performed to detect collagen type II (COL2A1), MMP13 and caspase-3 (CASP3) expression in cartilage tissues, and Safranin-O/Fast Green staining for cartilage damage. Alcian blue staining was performed to measure chondrogenic differentiation of BMSCs. Chondrocyte apoptosis was detected by using flow cytometry.
SAA treatment significantly attenuated cartilage damage in KOA model rats in a dose-dependent manner, and inhibited chondrocyte apoptosis induced by IL-1β in a dose-dependent manner. Moreover, SAA treatment promoted chondrogenesis-related proteins (COL2A1 and Aggrecan) expression and inhibited catabolism-related proteins (MMP13 and MMP3) expression both in the cartilage tissues from KOA model rat and in the IL-1β-treated chondrocytes. WD repeat domain 5 (WDR5) was a downstream target of SAA, and it facilitated chondrogenic differentiation of BMSCs derived from KOA model rats (KOA-BMSCs). Importantly, the inhibition of SAA treatment to the apoptosis and catabolism of chondrocyte and the promotion of SAA treatment to chondrogenic differentiation of KOA-BMSCs were rescued by silencing WDR5.
Overall, SAA treatment could facilitate cartilage repair via inhibiting the apoptosis and catabolism of chondrocyte and promoting chondrogenic differentiation of KOA-BMSCs by promoting WDR5 expression. Our data suggested that SAA may a potential drug for the treatment of KOA.
本研究旨在探讨丹酚酸A（SAA）对骨间充质干细胞（BMSCs）软骨分化的调控作用及其对膝骨关节炎（KOA）模型大鼠软骨修复的影响和作用机制。
采用免疫组织化学法检测软骨组织中II型胶原（COL2A1）、基质金属蛋白酶13（MMP13）和半胱天冬酶3（CASP3）的表达，并用番红O/固绿染色评估软骨损伤情况。采用阿尔辛蓝染色法检测BMSCs的软骨分化情况。采用流式细胞术检测软骨细胞凋亡情况。
SAA治疗以剂量依赖方式显著减轻KOA模型大鼠的软骨损伤，并以剂量依赖方式抑制IL-1β诱导的软骨细胞凋亡。此外，SAA治疗可促进KOA模型大鼠软骨组织和IL-1β处理的软骨细胞中软骨生成相关蛋白（COL2A1和聚集蛋白聚糖）的表达，并抑制分解代谢相关蛋白（MMP13和MMP3）的表达。WD重复结构域5（WDR5）是SAA的下游靶点，它促进了KOA模型大鼠来源的BMSCs（KOA-BMSCs）的软骨分化。重要的是，通过沉默WDR5可挽救SAA治疗对软骨细胞凋亡和分解代谢的抑制作用以及SAA治疗对KOA-BMSCs软骨分化的促进作用。
总体而言，SAA治疗可通过抑制软骨细胞凋亡和分解代谢，并通过促进WDR5表达促进KOA-BMSCs软骨分化，从而促进软骨修复。我们的数据表明SAA可能是一种治疗KOA的潜在药物。
