类风湿性关节炎（RA）中，过增殖的成纤维细胞样滑膜细胞（FLS）可分泌多种组织水解酶，如基质金属蛋白酶（MMPs），导致软骨细胞的破坏。间充质干细胞（MSC）可通过胞外囊泡（EVs）直接影响FLS。白细胞介素-27（IL-27）是一种在RA中常见过表达的多效免疫调节剂。本研究旨在研究骨髓间充质干细胞（BM-MSCs）诱导的IL-27诱导的外泌体的作用，并确定它们是否促进滑膜细胞中MMP3的分泌。研究团队进行了基因研究。该研究在中国海南省海口市海南医学院第一附属医院进行。研究团队：（1）确定是否在滑膜液中发生了IL-27表达；（2）将IL-27诱导的MSC与FLS共培养以检测FLS中MMP3的表达（3）在IL-27诱导下，收集IL-27R基因沉默的MSC源外泌体以检测与RA相关的微小RNA（miRNAs）的表达；（4）筛选miRNAs以确定表达中最显著的差异；（5）使用Western blot（WB）和qRT-PCR确定关节炎的miRNA靶基因；和（6）双荧光素酶和ChIP实验证实L3MBTL4通过调节MMP3。IL-27在RA中高表达，IL-27诱导的MSC源外泌体促进FLS中MMP3的表达。IL-27诱导的MSC源外泌体显著上调了miR-206-3p的表达，而miR-206-3p的靶基因miR-206/致命（3）恶性脑肿瘤样蛋白4（L3MBTL4）调节了MMP3的转录。IL-27诱导的MSC源外泌体通过miR-206-3p/L3MBTL4轴促进FLS中MMP3的表达，从而促进软骨细胞的降解并加重RA。IL-27可以诱导MSC中miR-206的表达，并且miR-206可以通过MSC-EVs传输到FLS中促进FLS迁移和MMP3的表达并加重关节软骨的损伤。具有高IL-27表达的RA患者可能不适宜接受MSC治疗，临床医生可以使用沉默或删除IL-27R的MSC来治疗高IL-27表达的RA患者。

In rheumatoid arthritis (RA), hyperproliferative fibroblast-like synoviocytes (FLS) can secrete a variety of tissue hydrolases, such as matrix metalloproteinases (MMPs), causing the destruction of chondrocytes. Mesenchymal stem cells (MSCs) can directly affect FLS through extracellular vesicles (EVs). Interleukin-27 (IL-27) is a pleiotropic immune regulator frequently overexpressed in RA.The study intended to examine the effects of IL-27-induced exosomes from bone-marrow mesenchymal stem cells (BM-MSCs) and to determine if they promote the secretion of MMP3 in synovial cells.The research team performed a genetic study.The study took place at the First Affiliated Hospital of Hainan Medical University in Haikou City, Hainan, China.The research team: (1) determined if IL-27 expression had occurred in the synovial fluid; (2) co-cultured IL-27-induced MSCs with FLS to detect the expression of MMP3 in the FLS; (3) Under IL-27 induction, MSC-derived exosomes with IL-27R knockdown were collected to detect the expression of microRNAs(miRNAs) associated with RA; (4) screened the miRNAs to determine the most significant differences in expression; (5) determined the miRNA target genes in arthritis, using Western blot (WB) and qRT-PCR; and (6) Dual luciferase and ChIP experiments confirm regulation of MMP3 by L3MBTL4.IL-27 was highly expressed in RA, and the IL-27-induced, MSC-derived exosomes promoted the expression of MMP3 in FLS. The IL-27-induced MSC-derived exosomes significantly upregulated the expression of miR-206-3p, and the miR-206-3p target, miR-206/ lethal(3) malignant brain tumor-like protein 4 (L3MBTL4), regulated the MMP3 transcription. The IL-27-induced, MSC-derived exosomes promoted MMP3 expression in the FLS through the miR-206-3p/L3MBTL4 axis, thereby promoting chondrocyte degradation and aggravating RA.IL-27 can induce the expression of miR-206 in MSCs, and miR-206 can be transported into FLS through MSC-EVs to promote FLS migration and MMP3 expression and aggravate articular cartilage damage. Patients with RA who have a high IL-27 expression may not be suitable to receive treatment with MSCs, and clinicians can use MSCs that knock down or delete IL-27R to treat RA patients who have a high IL-27 expression.