Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis

He, Lei; He, Tianwei; Xing, Jianghao; Zhou, Qing; Fan, Lei; Liu, Can; Chen, Yuyong; Wu, Depeng; Tian, Zhenming; Liu, Bin; Rong, Limin

doi:10.1186/s13287-020-01781-w

Cited by 211 publications

(178 citation statements)

References 53 publications

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“… 8 Bone marrow-derived mesenchymal stem cells (BM-MSCs)-released exosomes have been reported to be able to protect cartilage against damage and mitigate knee OA pain in a rat model. 9 Evidence has emphasized that microRNA (miRNA) and exosomes are beneficial for early diagnosis and are the useful treatment of OA. 10 miRNAs invariably serve as either onco‐miRNAs or tumor‐suppressor miRNAs for different biological processes, and their roles are primarily based on its downstream genes.…”

Section: Introductionmentioning

confidence: 99%

Exosome-Encapsulated microRNA-127-3p Released from Bone Marrow-Derived Mesenchymal Stem Cells Alleviates Osteoarthritis Through Regulating CDH11-Mediated Wnt/β-Catenin Pathway

Dong¹,

Li²,

Fang³

et al. 2021

JPR

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Exosome-encapsulated microRNAs (miRNAs) are being considered as either diagnostic or predictive markers in different types of diseases. Here, we discussed the effects of exosome-encapsulated miR-127-3p from bone marrow-derived mesenchymal stem cells (BM-MSCs) on osteoarthritis (OA). Methods: BM-MSCs and primary chondrocytes were isolated from Sprague Dawley rats. IL-1β was utilized to treat chondrocytes to mimic an OA in vitro model, and exosomes extracted from BM-MSCs were utilized to treat chondrocytes so as to verify their protective effects on OA. Through online website prediction and experiments confirmation, we found the most significantly enriched miRNA in exosomes and elucidated the effect of this miRNA on the therapeutic effect of exosomes by interfering with its expression. Also, the genes targeted by the miRNA and the involved pathway were also found through bioinformatics analysis and experimental research, thereby probing into the protective mechanism of exosomes on chondrocytes. Results: Exosomes derived from BM-MSCs restricted the IL-1β-induced chondrocytes damage. miR-127-3p was found to be enriched in exosomes, and the protective effect of exosomes was reversed by miR-127-3p inhibition. miR-127-3p targeted CDH11, and overexpressed CDH11 in chondrocytes weakened the therapeutic effect of exosomes. IL-1β treatment resulted in the activation of the Wnt/β-catenin pathway in chondrocytes. Exosomes treatment could inhibit the activation of this pathway, and overexpressed CDH11 reversed the inhibitory effect of exosomes on this pathway. Conclusion: This study suggests that exosomal miR-127-3p derived from BM-MSCs inhibits CDH11 in chondrocytes, thereby blocking the Wnt/β-catenin pathway activation and relieving chondrocyte damage in OA.

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Section: Introductionmentioning

confidence: 99%

Exosome-Encapsulated microRNA-127-3p Released from Bone Marrow-Derived Mesenchymal Stem Cells Alleviates Osteoarthritis Through Regulating CDH11-Mediated Wnt/β-Catenin Pathway

Dong¹,

Li²,

Fang³

et al. 2021

JPR

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“…We found that MSCs were the most widely applied cells and the research focused on the process of cartilage repair and exosome secretion. inhibited the in ammatory response and repaired injured cartilage 18,19 . Small RNAs in exosomes decrease the expression of in ammatory factors and improve oxidative stress states 20,21 .…”

Section: Discussionmentioning

confidence: 99%

The 100 Most Cited Articles on the Applications of Stem Cells in Osteoarthritis: A Bibliometric Analysis

Yang¹,

Zhou²,

Lin

2020

Preprint

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Background: Stem cells have been applied in the treatment of OA, which had attracted wide attention. However, the research area is relatively extensive, and the research level is variable. In this study, we reviewed the mechanisms and clinical applications of stem cells in OA by using bibliometric analysis for the first time. We also revealed the characteristics, superior results and developmental trends in this field.Methods: The Web of Science core collection database was used to search articles related to the application of stem cells in OA. We collected the general information from the top 100 cited articles. We analyzed and evaluated the articles according to publication number, journals, institutions, countries, keywords and extended keywords.Results: The 100 most cited articles were cited from 129 to 1353 times mainly reviews and original articles. These articles were published from 2001 to 2017 and distributed evenly in America, East Asia and European countries. The United States contributed most in published number and international cooperation. The top ten institutions are mainly major universities and Duke University published a maximum of 10 articles. In terms of journals ,57 articles were published in the top ten journals. The keywords were divided into 8 categories from molecular mechanisms to clinical application.Conclusions: In our study, we found that mesenchymal stem cells (MSCs) which could repair articular cartilage and inhibit local inflammation, are the most widely applied in research and treatment of OA. TGF-βwas crucial during the process. Exosomes are regarded as the active ingredients in stem cell therapy for OA. Microtissue engineering will contribute to accurate and effective stem cell therapy. The findings of our study will contribute to the continuous development of research and direct the research of stem cells in OA.

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“…The EVs also inhibited M1 macrophage infiltration and reduced IL-1β-positive cells in the synovium [ 127 ]. A recent study showed that EVs from rat BM-MSCs reduced MMP-13 expression in rat chondrocytes and reduced serum levels of IL-1β, IL-6, and TNF-α in vivo [ 128 ].…”

Section: Therapeutic Effects Of Evs On Inflammatory Diseasesmentioning

confidence: 99%

Therapeutic Application of Exosomes in Inflammatory Diseases

Suh

Joo

Hong

et al. 2021

IJMS

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Immunomodulation is on the cusp of being an important therapy for treating many diseases, due to the significant role of the immune system in defending the human body. Although the immune system is an essential defense system, overactivity can result in diverse sicknesses such as inflammation and autoimmune disease. Exosomes are emerging as a state-of-the-art therapeutic strategy for treating an overactive immune system. Thus, in this review, we will thoroughly review therapeutic applications of exosomes in various inflammatory and autoimmune diseases. Finally, issues for an outlook to the future of exosomal therapy will be introduced.

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Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis

Cited by 211 publications

References 53 publications

Exosome-Encapsulated microRNA-127-3p Released from Bone Marrow-Derived Mesenchymal Stem Cells Alleviates Osteoarthritis Through Regulating CDH11-Mediated Wnt/β-Catenin Pathway

Exosome-Encapsulated microRNA-127-3p Released from Bone Marrow-Derived Mesenchymal Stem Cells Alleviates Osteoarthritis Through Regulating CDH11-Mediated Wnt/β-Catenin Pathway

The 100 Most Cited Articles on the Applications of Stem Cells in Osteoarthritis: A Bibliometric Analysis

Therapeutic Application of Exosomes in Inflammatory Diseases

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