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

Chongzhi Pan,Tianlong Wu,Wenzhou Huang,Xigao Cheng,Jiu Xu,Guoyu Yao,Bin Li,Changchang Yin,Qi Chen

doi:10.3389/fbioe.2021.772002

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.

Highlights

Osteoarthritis (OA) is one of the most common age-related degenerative joint diseases and public health problems worldwide, and can cause pain, disability, social and economic loss (Glyn-Jones et al, 2015)
Following establishment of the vitro OA model, chondrocytes were treated with normal medium, Human MSCs (hMSCs)-EVs (10 μg/ml), and hMSCsmalat−1-EVs (EVs derived from lncRNA malat-1overexpressing-hMSCs) for 24 h to investigate the effect of EVs, derived from lncRNA malat-1-overexpressing-hMSCs, on IL-1β-induced chondrocyte damage
These results show that EVs were successfully separated from the hMSCs

Summary

Introduction

Osteoarthritis (OA) is one of the most common age-related degenerative joint diseases and public health problems worldwide, and can cause pain, disability, social and economic loss (Glyn-Jones et al, 2015). OA is characterized by the destruction of articular cartilage, synovial inflammation, osteophyte formation, and extracellular matrix (ECM) loss (Guilak et al, 2018). It is a clinical priority to seek new treatments for OA. Apoptosis and of extracellular matrix loss might represent new therapeutic avenues for the management and treatment of OA. Existing animal experiments and clinical studies have confirmed that intra-articular injection of MSCs can effectively delay the degeneration of articular cartilage, relieve pain and improve joint function (Desando et al, 2013; Matas et al, 2019). MSCs treatment still has certain limitations and side effects, such as thrombosis (Furlani et al, 2009) and abnormal ossification (Breitbach et al, 2007).

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