LncRNA Malat-1 From MSCs-Derived Extracellular Vesicles Suppresses Inflammation and Cartilage Degradation in Osteoarthritis

Abstract

Purpose: Extracellular Vesicles (EVs) derived from hMSCs, have the potential to alleviate cartilage damage and inflammation. We aimed to explore the effects of EVs derived from lncRNA malat‐1-overexpressing human mesenchymal stem cells (hMSCs) on chondrocytes.Material and Methods: hMSCs-derived Extracellular Vesicles (hMSCs-EVs) were identified by transmission electron microscopy and western blot. We used a Sprague-Dawley (SD) rat model of CollagenaseⅡ-induced osteoarthritis (OA) as well as IL-1β-induced OA chondrocytes. Lentiviral vectors were used to overexpress lncRNA malat‐1 in hMSCs. Chondrocyte proliferation, inflammation, extracellular matrix degradation, and cell migration were measured by Edu staining, ELISA, western blot analysis, and transwell assay. Chondrocyte apoptosis was evaluated by flow cytometry, Hoechst 33342/PI Staining, and western blot. Safranine O-fast green (S-O) staining and HE staining were used to assess morphologic alterations of the rat knee joint.Results: hMSCsmalat−1-EVs decreased MMP-13, IL-6, and Caspase-3 expression in IL-1β-induced OA chondrocytes. Moreover, hMSCsmalat−1-EVs promoted chondrocyte proliferation and migration, suppressed apoptosis, and attenuated IL-1β-induced chondrocyte injury. Our animal experiments suggested that hMSCsmalat−1-EVs were sufficient to prevent cartilage degeneration.Conclusion: Our findings show that lncRNA malat-1from hMSCs‐delivered EVs can promote chondrocyte proliferation, alleviate chondrocyte inflammation and cartilage degeneration, and enhance chondrocyte repair. Overall, hMSCsmalat−1-EVs might be a new potential therapeutic option for patients with OA.

Extracellular Vesicles as Communicators of Senescence in Musculoskeletal Aging

“…Exogenous application of MALAT1 in EVs can reduce inflammation and joint degeneration in an experimental model of OA. (69) Together these findings suggest that interventions to increase MALAT1 in multiple tissues may have beneficial effects by sponging miR-34a or suppressing its expression (Fig. 3).…”

Emerging role of lncRNAs in osteoarthritis: An updated review

“…Zhang and colleagues also reported that targeting lncRNA NEAT1 through artificial exosomes could be one of the options to elevate chondrocyte proliferation for OA treatment ( 196 ). Pan and colleagues confirmed the effect of MALAT1 on chondrocytes, which exhibited a slight cartilage damage and a smooth surface after intra-articular injection of LAMAT1 extracellular vesicles in OA animal model ( 179 ). In addition, the use of nanoparticles as an effective delivery vehicle for targeting lncRNAs provides a new therapeutic strategy owing to improved stability, biocompatibility, and high-dose therapeutic payloads ( 197 ).…”

“…Overexpression of MALAT1 in human chondrocytes inhibited cells viability and promoted cartilage ECM degradation through targeting miR145 ( 35 ). Also, lncRNA MALAT1 overexpression in human C28/I2 chondrocyte cells was proved to promote chondrocyte migration, inflammation suppression, and ECM degradation ( 179 ). Besides, MALAT1 could act as sponges for other miRNAs, like miR127-5p ( 36 ), miR150-5p ( 180 ) and miR146a ( 181 ), thus likely to play some regulatory roles in OA cartilage.…”

Allelic expression imbalance in articular cartilage and subchondral bone refined genome-wide association signals in osteoarthritis

“…In addition, as we suggested above, the lncRNA MALAT1 appears to have an important role in OA. MALAT1 in chondrocytes promotes chondrocyte proliferation, suppress chondrocyte apoptosis and reduces extracellular matrix degradation (29,30). Recently, the use of Revesratrol to suppress the activation of MALAT1 showed a decreased of pro-inflammatory genes (NF-κB1 and IL-6) by modulating a microRNA (miR-9) (31).…”