Bone marrow mesenchymal stem cell-derived extracellular vesicles containing miR-497-5p inhibit RSPO2 and accelerate OPLL

• DOI: 10.1016/j.lfs.2021.119481
• Publication Date: 2021-04-13T04:19:15Z
• Authors: Xiaohui Chen; Shengxing Wang; Zhan Cui; Yutong Gu
• Keywords: 0301 basic medicine; Cell Differentiation; Mesenchymal Stem Cells; Ossification of Posterior Longitudinal Ligament; Rats; Extracellular Vesicles; MicroRNAs; 03 medical and health sciences; Gene Expression Regulation; Animals; Humans; Rats, Wistar; Thrombospondins

Muscle and adipose tissue-derived mesenchymal stem cells presented high osteogenic potentials, which modulate osteoblast function through releasing extracellular vesicles (EVs) containing miRNAs. Herein, this study evaluated the function of bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) delivering miR-497-5p in ossification of the posterior longitudinal ligament (OPLL).The expression level of miR-497-5p was validated in ossified posterior longitudinal ligament (PLL) tissues and BMSC-EVs. The uptake of BMSC-EVs by ligament fibroblasts was observed by immunofluorescence. miR-497-5p was overexpressed or downregulated to assess its role in osteogenic differentiation of ligament fibroblasts. Further, an OPLL rat model was established to substantiate the effect of BMSC-EVs enriched with miR-497-5p on OPLL.Ossified PLL tissues presented with high miR-497-5p expression. PLL fibroblasts were identified to endocytose BMSC-EVs. BMSC-EVs could upregulate miR-497-5p and shuttle it to ligament fibroblasts to accelerate the osteogenic differentiation. miR-497-5p targeted and inversely regulated RSPO2. Then, RSPO2 overexpression activated Wnt/β-catenin pathway and repressed the osteogenic differentiation of ligament fibroblasts. In vivo experiments further showed that miR-497-5p-containing BMSC-EVs enhanced OPLL through diminishing RSPO2 and inactivating Wnt/β-catenin pathway.BMSC-EVs could deliver miR-497-5p to ligament fibroblasts and modulate RSPO2-mediated Wnt/β-catenin pathway, thereby accelerating OPLL.