Cyaonoside A (CyA), derived from the natural Chinese medicine, Cyathula officinalis Kuan, which was for a long time used to treat knee injuries and relieve joint pain in traditional Chinese medicine, showed an unclear mechanism for protecting cartilage. In addition, CyA was poorly hydrosoluble and incapable of being injected directly into the joint cavity, which limited its clinical application. This study reveals that CyA resisted IL-1β-mediated chondrogenic inflammation and apoptosis. Next, transcriptome sequencing is used to explore the potential mechanisms underlying CyA regulation of MSC chondrogenic differentiation. Based on these findings, CyA-loaded composite hydrogel microspheres (HLC) were developed and they possessed satisfactory loading efficiency, a suitable degradation rate and good biocompatibility. HLC increased chondrogenic anabolic gene (Acan, COL2A, and SOX9) expression, while downregulating the expression of the catabolic marker MMP13 in vitro. In the osteoarthritis mouse model, HLC demonstrated promising therapeutic capabilities by protecting the integrity of articular cartilage. In conclusion, this study provides insights into the regulatory mechanisms of CyA for chondrocytes and proposes a composite hydrogel microsphere-based advanced therapeutic strategy for osteoarthritis.

中文翻译：

---

负载氰皂苷A的复合水凝胶微球通过减轻软骨细胞炎症来治疗骨关节炎

氰皂苷A（CyA）源自天然中药川牛膝，中药长期以来用于治疗膝关节损伤和缓解关节疼痛，但其保护软骨的机制尚不清楚。此外，CyA水溶性差，无法直接注射到关节腔内，限制了其临床应用。这项研究表明 CyA 可以抵抗 IL-1β 介导的软骨形成炎症和细胞凋亡。接下来，利用转录组测序来探索 CyA 调节 MSC 软骨分化的潜在机制。基于这些发现，开发了负载CyA的复合水凝胶微球（HLC），它们具有令人满意的负载效率、合适的降解率和良好的生物相容性。 HLC 增加软骨合成代谢基因（Acan、COL2A 和 SOX9）的表达，同时在体外下调分解代谢标记物 MMP13 的表达。在骨关节炎小鼠模型中，HLC 通过保护关节软骨的完整性表现出有前景的治疗能力。总之，本研究深入了解了 CyA 对软骨细胞的调节机制，并提出了一种基于复合水凝胶微球的骨关节炎先进治疗策略。