Abstract
Excessive chondrocyte degeneration and inflammation are the pathological features of osteoarthritis (OA), and altered miR-212-5p may contribute to meniscus and cartilage degeneration. Whether exosomes derived from miR-212-5p overexpressed synovial mesenchymal stem cells (SMSC-212-5p-Exos) could be utilized to treat degenerative chondrocytes is investigated in this study. Down-regulated miR-212-5p and up-regulated E74 Like ETS Transcription Factor 3 (ELF3) expression were detected in OA synovial tissues, which showed a negative correlation (r = −0.55, p = 0.002). miR-212-5p directly targeted ELF3 and regulated the relative expression of ELF3 in SMSCs as indicated by luciferase reporter assay and RT-PCR. The relative expression of ELF3, chondrocyte degeneration-related molecules, matrix metalloproteinase, and inflammatory molecules were detected in chondrocytes stimulated with interleukin (IL)-1β or co-incubated with SMSC-212-5p-Exos or SMSCs-derived exosomes (SMSC-Exos). IL-1β induced up-regulation of ELF3, down-regulation of degeneration molecules (Collagen II, Aggrecan, and Sox9), up-regulation of matrix metalloproteinase (MMP-1, MMP-3, and MMP-13), and up-regulation of inflammatory molecules (IL-6, MCP-1, TNF-α, COX-2, and iNOS) could be inhibited by SMSC-212-5p-Exos or SMSC-Exos administration. When compared with the SMSC-Exos, SMSC-212-5p-Exos showed more treatment benefits. All of these indicate that SMSC-212-5p-Exos could suppress chondrocyte degeneration and inflammation by targeting ELF3, which can be considered as a disease-modifying strategy.
Highlights
Osteoarthritis (OA) is a disease that comprises progressive cartilage degenerative and synovial membrane inflammation, having an increased frequency of osteophyte formation and subchondral bone sclerosis in the aging population (Hunter and Bierma-Zeinstra, 2019; Katz et al, 2021; Sharma, 2021)
Research has shown that exosomes derived from synovial mesenchymal stem cells (SMSC-Exos) have the potential to palliate the severity of interleukin (IL)-1β induced osteoarthritis (Wang et al, 2020; Qiu et al, 2021)
Spindle-like SMSCs were observed at passage 3 (P3) (Figure 2A), which could be induced into osteogenic cells confirmed by Alizarin Red S staining of calcium mineral deposits (Figure 2B) and induced into adipogenic cells confirmed by Oil Red O staining of small cytoplasmic lipid droplets (Figure 2C)
Summary
Osteoarthritis (OA) is a disease that comprises progressive cartilage degenerative and synovial membrane inflammation, having an increased frequency of osteophyte formation and subchondral bone sclerosis in the aging population (Hunter and Bierma-Zeinstra, 2019; Katz et al, 2021; Sharma, 2021). No curative treatment has been applied in the clinic, and joint replacement remains the most commonly applied and effective therapy for the disability. It is reported that chondrocytes size could be potentially used to assess disease progression (Gratal et al, 2019). Research has shown that exosomes derived from synovial mesenchymal stem cells (SMSC-Exos) have the potential to palliate the severity of interleukin (IL)-1β induced osteoarthritis (Wang et al, 2020; Qiu et al, 2021). Further research is urgent to confirm the effectiveness and feasibility of exosome-based therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
