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BMSCs-derived Mitochondria Improve Osteoarthritis by Ameliorating Mitochondrial Dysfunction and Promoting Mitochondrial Biogenesis in Chondrocytes

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Abstract

Bone marrow mesenchymal stem cells (BMSCs)—derived exosomes and microvesicles can effectively improve knee osteoarthritis. We found that microvesicles performed a superior effect on improving mitochondrial function in chondrocytes than exosomes, which may be related to the ability of microvesicles carrying active mitochondria to replace damaged ones in chondrocytes. This study investigated the therapeutic effect of direct mitochondrial transplantation (MT) on knee osteoarthritis. IL-1β stimulated the osteoarthritis phenotype of rat chondrocytes, and the effect of BMSCs-derived mitochondria transplantation was observed in vitro. Knee osteoarthritis rat model was established by collagenase induction to observe the effect of intra-articular injection of mitochondria. Results showed that the mitochondria of BMSCs could be ingested by rat chondrocytes via co-incubation in vitro, and significantly improved osteoarthritis phenotype and mitochondrial function, and inhibited chondrocytes apoptosis. In vivo, BMSCs-derived mitochondria could be ingested by cartilage via intra-articular injection, ameliorated pathological cartilage injury, suppressed inflammation, inhibited chondrocytes apoptosis, and improved osteoarthritis phenotype. In addition, MT promoted mitochondrial biogenesis in chondrocytes by activating PGC-1α signaling. All above results suggest that BMSCs-derived mitochondria transplantation ameliorates knee osteoarthritis by improving chondrocytes mitochondrial dysfunction and promoting mitochondrial biogenesis.

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Data Availability

All data generated or analyzed during this study are available from the corresponding author on request.

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Funding

This study was supported by the National Key R&D Program of China (2020YFC2005800), National Natural Science Foundation of China (81760408; 8156036), Jiangxi Provincial Department of Science and Technology Project (20181BCG42001) and Natural Science Foundation of Jiangxi Province (20113BCB22005).

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Author notes

  1. Mingchuan Yu and Di Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi, 330006, People’s Republic of China

    Mingchuan Yu, Di Wang, Xiang Chen, Da Zhong & Jun Luo

Authors
  1. Mingchuan Yu
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  2. Di Wang
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  3. Xiang Chen
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  4. Da Zhong
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  5. Jun Luo
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Contributions

MY: conception and design, performing research, and drafting the article. DW: performing research and revising the article. XC and DZ: acquisition of data, analysis and interpretation of data. JL: conception and approve of the manuscript.

Corresponding author

Correspondence to Jun Luo.

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Animal protocols were approved by the Ethics Committee of Nanchang University.

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Not applicable as it is not a clinical study.

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The authors declare no conflict of interest.

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This article belongs to the Topical Collection: Special Issue on Exosomes & Microvesicles: from Stem Cell Biology to Translation in Human Diseases

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Yu, M., Wang, D., Chen, X. et al. BMSCs-derived Mitochondria Improve Osteoarthritis by Ameliorating Mitochondrial Dysfunction and Promoting Mitochondrial Biogenesis in Chondrocytes. Stem Cell Rev and Rep 18, 3092–3111 (2022). https://doi.org/10.1007/s12015-022-10436-7

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