Mesenchymal stem cell-derived exosome mediated long non-coding RNA KLF3-AS1 represses autophagy and apoptosis of chondrocytes in osteoarthritis

Wen, Chuanyang; Lin, Lupan; Zou, R.; Lin, Fuqing; Liu, Yubao

doi:10.1080/15384101.2021.2019411

Cited by 27 publications

(17 citation statements)

References 38 publications

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“…EXOs from human urine-derived stem cells (hUSCs) are capable of inducing proliferation and migration in chondrocytes [ 37 ]. Moreover, human MSCs-EXOs were found to inhibit autophagy and apoptosis in chondrocytes by activating the axis of PI3K/Akt/mTOR [ 38 ]. Mitochondria are the power supply center of the cell, providing ATP in many key biological events, such as cell growth, differentiation, and migration [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Human Bone Marrow Mesenchymal Stem Cell-Derived Exosomes on Cartilage Repair in Rabbits

Yang

Huang

et al. 2022

Stem Cells International

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Mesenchymal stem cells (MSCs) have shown chondroprotective effects in cartilage repair. However, side effects caused by MSC treatment limit their application in clinic. As a cell-free therapy, MSC-derived exosomes (EXOs) have attracted much more attention in recent years. In the present study, we prepared EXOs from human bone marrow mesenchymal stem cells (hBMSCs) and examined their therapeutic potentials in cartilage repair. Our results showed that the prepared extracellular vesicles exhibit classical features of EXOs, such as cup-like shape, around 100 nm diameter, positive protein markers (CD81, TSG101, and Flotillin 1), and ability of internalization. In primary chondrocytes, the treatment of hBMSC-EXOs markedly increases cell viability and proliferation in a dose-dependent manner. Moreover, wound healing assay showed that hBMSC-EXOs accelerate cell migration in primary chondrocytes. JC-1 staining revealed that the mitochondrial membrane potential was enhanced by hBMSC-EXOs, indicating cell apoptosis was decreased in the presence of hBMSC-EXOs. In rabbits with articular cartilage defects, local administration with hBMSC-EXOs facilitates cartilage regeneration as evidenced by gross view and hematoxylin-eosin (H&E) and Saf-O/Fast Green staining. In addition, the International Cartilage Repair Society (ICRS) score was increased by the application of hBMSC-EXOs. Overall, our data indicate that the treatment with hBMSC-EXOs is a suitable cell-free therapy for treating cartilage defects, and these benefits are likely due to improved cell proliferation and migration in chondrocytes.

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Section: Discussionmentioning

confidence: 99%

The Effect of Human Bone Marrow Mesenchymal Stem Cell-Derived Exosomes on Cartilage Repair in Rabbits

Yang

Huang

et al. 2022

Stem Cells International

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“…In recent years, mesenchymal stem cell-derived sEV have been found to promote the proliferation and migration of many different types of cells in vitro , such as chondrocytes ( Wen et al, 2022 ), vascular endothelial cells ( Zhang et al, 2021 ), neuronal cells ( Wei et al, 2020 ), keratinocytes ( Kim et al, 2018 ), and fibroblasts ( Shabbir et al, 2015 ). In view of the key role of sEV in boosting the regeneration and repair of different tissues, we speculate that UCMSC-sEV may also affect the repair of urethral tissue injury by affecting the biological behaviors of PUSMCs (such as proliferation and migration).…”

Section: Discussionmentioning

confidence: 99%

CD73-Positive Small Extracellular Vesicles Derived From Umbilical Cord Mesenchymal Stem Cells Promote the Proliferation and Migration of Pediatric Urethral Smooth Muscle Cells Through Adenosine Pathway

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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Smooth muscle cells (SMCs) are the main functional component of urethral tissue, but are difficult to proliferate in vitro. Mesenchymal stem cells (MSCs) and mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have been shown to promote tissue repair by regulating the proliferation and migration of different types of cells. In this study, we investigated the effect of umbilical cord mesenchymal stem cell-derived sEV (UCMSC-sEV) on the proliferation and migration of pediatric urethral smooth muscle cells (PUSMCs) and the mechanism by which sEV regulates the function of PUSMCs. We observed that UCMSC-sEV can significantly promote the proliferation and migration of PUSMCs in vitro. UCMSC-sEV exerted proliferation and migration promotion effects by carrying the CD73 to PUSMCs and catalyzing the production of adenosine. Conversely, the effect of UCMSC-sEV on the proliferation and migration of PUSMCs were no longer observed with addition of the PSB12379 as a CD73 inhibitor. It was found that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in PUSMCs was activated by adenosine or UCMSC-sEV intervention. In summary, UCMSC-sEV promoted proliferation and migration of PUSMCs in vitro by activating CD73/adenosine signaling axis and downstream PI3K/AKT pathway. Thus, we concluded that UCMSC-sEV may be suggested as a new solution strategy for the urethral tissue repair.

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“…found that human mesenchymal stem cell-derived exosomes (MSC-Exo) upregulated KLF3-AS1 expression, then activated the PI3K/Akt/mTOR signaling pathway and finally inhibited autophagy, mediated by lncRNA (KLF3-AS1). Then, MSC-Exo were found to reduce chondrocyte apoptosis and improve OA symptoms, which is expected to be a potential target for OA therapy [ 158 ]. As a novel scavenger of ROS and reactive nitrogen species, dopamine melanin (DM) nanoparticles possess low cytotoxicity and a powerful ability to sequester ROS and reactive nitrogen species.…”

Section: Reviewmentioning

confidence: 99%

Autophagy in the pathogenesis and therapeutic potential of post-traumatic osteoarthritis

Gong

et al. 2023

Burns &Amp; Trauma

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Autophagy, as a fundamental mechanism for cellular homeostasis, is generally involved in the occurrence and progression of various diseases. Osteoarthritis (OA) is the most common musculoskeletal disease that often leads to pain, disability and economic loss in patients. Post-traumatic OA (PTOA) is a subtype of OA, accounting for >12% of the overall burden of OA. PTOA is often caused by joint injuries including anterior cruciate ligament rupture, meniscus tear and intra-articular fracture. Although a variety of methods have been developed to treat acute joint injury, the current measures have limited success in effectively reducing the incidence and delaying the progression of PTOA. Therefore, the pathogenesis and intervention strategy of PTOA need further study. In the past decade, the roles and mechanisms of autophagy in PTOA have aroused great interest in the field. It was revealed that autophagy could maintain the homeostasis of chondrocytes, reduce joint inflammatory level, prevent chondrocyte death and matrix degradation, which accordingly improved joint symptoms and delayed the progression of PTOA. Moreover, many strategies that target PTOA have been revealed to promote autophagy. In this review, we summarize the roles and mechanisms of autophagy in PTOA and the current strategies for PTOA treatment that depend on autophagy regulation, which may be beneficial for PTOA patients in the future.

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Mesenchymal stem cell-derived exosome mediated long non-coding RNA KLF3-AS1 represses autophagy and apoptosis of chondrocytes in osteoarthritis

Cited by 27 publications

References 38 publications

The Effect of Human Bone Marrow Mesenchymal Stem Cell-Derived Exosomes on Cartilage Repair in Rabbits

The Effect of Human Bone Marrow Mesenchymal Stem Cell-Derived Exosomes on Cartilage Repair in Rabbits

CD73-Positive Small Extracellular Vesicles Derived From Umbilical Cord Mesenchymal Stem Cells Promote the Proliferation and Migration of Pediatric Urethral Smooth Muscle Cells Through Adenosine Pathway

Autophagy in the pathogenesis and therapeutic potential of post-traumatic osteoarthritis

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