Rheumatoid arthritis (RA) is a severe autoimmune disease with symptoms including synovial inflammation, cartilage erosion, and bone loss in RA lesions, which eventually lead to joint deformity and function loss. Most current treatments fail to achieve satisfying therapeutic outcomes with some adverse effects. Extracellular vesicles derived from apoptotic cells (apoEVs) have emerged as important mediators in intercellular communication regulating diverse physiological and pathological processes. In this study, we investigated the therapeutic efficacy of macrophage-derived and osteoclast-derived apoEVs (Mφ-apoEVs and OC-apoEVs) on RA. The results showed that both Mφ-apoEVs and OC-apoEVs induced macrophage repolarization toward the anti-inflammatory M2 phenotype, promoted chondrocyte functions and chondrogenesis, and inhibited osteoclast formation and maturation. In addition, OC-apoEVs promoted osteogenic differentiation. The study on the CIA mouse model further demonstrated that apoEVs could couple various functions and exert synergistic effects on the joint with RA, as evidenced by the regression of synovial inflammation, the reversal of cartilage damage and bone erosion, and the preservation of joint structure. These findings demonstrated that Mφ-apoEVs and OC-apoEVs contributed to restoring the homeostasis of the overall microenvironment in the RA joint and highlighted their potential application as a promising alternative to treat RA.

中文翻译：

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凋亡细胞外囊泡恢复关节微环境稳态以治疗类风湿性关节炎

类风湿性关节炎（RA）是一种严重的自身免疫性疾病，其症状包括RA病变处的滑膜炎症、软骨侵蚀和骨质流失，最终导致关节畸形和功能丧失。目前大多数治疗方法未能达到令人满意的治疗效果，并伴有一些副作用。源自凋亡细胞（apoEV）的细胞外囊泡已成为调节多种生理和病理过程的细胞间通讯的重要介质。在本研究中，我们研究了巨噬细胞来源和破骨细胞来源的 apoEV（Mφ-apoEV 和 OC-apoEV）对 RA 的治疗效果。结果表明，Mφ-apoEVs和OC-apoEVs均诱导巨噬细胞向抗炎M2表型复极化，促进软骨细胞功能和软骨形成，并抑制破骨细胞形成和成熟。此外，OC-apoEVs 促进成骨分化。 CIA小鼠模型的研究进一步表明，apoEVs可以耦合多种功能，对RA关节发挥协同作用，表现为滑膜炎症的消退、软骨损伤和骨质侵蚀的逆转以及关节结构的保存。这些发现表明，Mφ-apoEVs 和 OC-apoEVs 有助于恢复 RA 关节整体微环境的稳态，并强调了它们作为治疗 RA 的有希望的替代方案的潜在应用。