Journal
CELL BIOLOGY AND TOXICOLOGY
Volume 37, Issue 1, Pages 85-96Publisher
SPRINGER
DOI: 10.1007/s10565-020-09559-9
Keywords
Osteoarthritis; Synovial mesenchymal stem cells; Exosomes; miR-155-5p; Runx2
Categories
Funding
- National Natural Science Foundation of China [81873990, 81873991, 81672238]
- Jiangsu Provincial Medical Youth Talent [QNRC2016751]
- Natural Science Foundation of Jiangsu Province [BK20180001]
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The study demonstrated that miR-155-5p-overexpressing SMSC-Exos could attenuate OA-induced injury by promoting ECM secretion. SMSC-Exos enhanced proliferation and migration, suppressed apoptosis of osteoarthritic chondrocytes, but had no effect on ECM secretion.
Synovial mesenchymal stem cells (SMSCs) have the potential to attenuate osteoarthritis (OA)-induced injury. The role and mechanism of SMSC-derived exosomes (SMSC-Exos), pivotal paracrine factors of stem cells, in OA-associated injury remain unclear. We aimed to confirm the effect of SMSC-Exos with specific modifications on OA-induced damage and to investigate the potential molecular mechanisms. Exosomes derived from miR-155-5p-overexpressing SMSCs (SMSC-155-5p-Exos) and SMSCs (SMSC-Exos) were isolated and characterized. CCK-8, Transwell, and Western blot analyses were used to detect proliferation, migration, extracellular matrix (ECM) secretion, and apoptosis of osteoarthritic chondrocytes. The therapeutic effect of exosomes in a mouse model of OA was examined using immunohistochemical staining and OARSI scores. SPSS 17.0 and GraphPad software were used for all statistical analyses in this study. The SMSC-Exos enhanced the proliferation and migration and inhibited the apoptosis of osteoarthritic chondrocytes but had no effect on ECM secretion. The miR-155-5p-overexpressing exosomes showed common characteristics of exosomes in vitro and further promoted ECM secretion by targeting Runx2. Thus, the SMSC-155-5p-Exos promoted proliferation and migration, suppressed apoptosis and enhanced ECM secretion of osteoarthritic chondrocytes, and effectively prevented OA in a mouse model. In addition, overexpression of Runx2 partially reversed the effect of the SMSC-155-5p-Exos on osteoarthritic chondrocytes. Given the insufficient effect of the SMSC-Exos on the ECM secretion of osteoarthritic chondrocytes, we modified the SMSM-Exos and demonstrated that the SMSC-155-5p-Exos could prevent OA. Exosomes derived from modified SMSCs may be a new treatment strategy to prevent OA.
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