Monocyte-derived cells were shown to promote cartilage repair in osteoarthritis. The role of the long non-coding RNA (lncRNA) MM2P in this function of monocyte-derived cells remained unexplored. Treatment of RAW264.7 murine macrophages and mouse bone marrow-derived macrophages with IL-4 or IL-13 upregulated MM2P expression, upstream of STAT3 and STAT6 phosphorylation. Specifically, MM2P blocked SHP2-mediated dephosphorylation of STAT3 at Try705 and interacted with the RNA-binding protein FUS. In turn, p-STAT3 increased the Sox9 gene expression. These cells released Sox9 mRNA and protein-containing exosomes, as demonstrated by a transmission electron microscope, nanoparticle tracking analysis, and detection of typical surface markers. Their culture supernatant promoted the differentiation of mouse primary chondrocytes, i.e., upregulated the expression of Col1a2 and Acan genes and promoted the secretion of extracellular matrix components proteoglycan and type II collagen. These effects were mediated by Sox9 mRNA and protein delivered to chondrocytes by exosomes. Together, ex vivo treatment of monocyte-derived cells with IL-4 or IL-13 promoted chondrocyte differentiation and functions through exosome-mediated delivery of Sox9 mRNA and protein.

单核细胞衍生的细胞被证明可以促进骨关节炎的软骨修复。长链非编码 RNA (lncRNA) MM2P 在单核细胞衍生细胞的这种功能中的作用仍未得到探索。用 IL-4 或 IL-13 处理 RAW264.7 鼠巨噬细胞和小鼠骨髓来源的巨噬细胞可上调 STAT3 和 STAT6 磷酸化上游的 MM2P 表达。具体来说，MM2P 在 Try705 阻止了 SHP2 介导的 STAT3 去磷酸化，并与 RNA 结合蛋白 FUS 相互作用。反过来，p-STAT3 增加了 Sox9 基因的表达。这些细胞释放了 Sox9 mRNA 和含有蛋白质的外泌体，如透射电子显微镜、纳米粒子追踪分析和典型表面标记的检测所证明的那样。他们的培养上清液促进了小鼠原代软骨细胞的分化，即，上调 Col1a2 和 Acan 基因的表达，促进细胞外基质成分蛋白多糖和 II 型胶原蛋白的分泌。这些作用是由外泌体传递到软骨细胞的 Sox9 mRNA 和蛋白质介导的。总之，用 IL-4 或 IL-13 对单核细胞衍生细胞的离体处理通过外泌体介导的 Sox9 mRNA 和蛋白质的传递促进了软骨细胞分化和功能。