tsRNA-12391-Modified Adipose Mesenchymal Stem Cell-Derived Exosomes Mitigate Cartilage Degeneration in Osteoarthritis by Enhancing Mitophagy

IF 3.2 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS
Jingsheng Shi, Guanglei Zhao, Siqun Wang, Yibing Wei, Jianguo Wu, Gangyong Huang, Jie Chen, Jun Xia
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引用次数: 0

Abstract

Osteoarthritis (OA) is a cartilage-degenerative joint disease. Mitophagy impacts articular cartilage damage. tRNA-derived small RNAs (tsRNAs) are one of the contents of adipose mesenchymal stem cell (AMSC)-derived exosomes (AMSC-exos) and are involved in disease progression. However, whether tsRNAs regulate mitophagy and whether tsRNA-modified AMSC-exos improve OA via mitophagy remain unclear. We performed small RNA sequencing to identify OA-related tsRNAs, which were then loaded into AMSC-exos, exploring the function and mechanisms related to mitophagy in vitro and in vivo. Overall, 53 differentially expressed tsRNAs (DEtsRNAs) were identified between OA and normal cartilage tissues, among which 42 DEtsRNAs, including tsRNA-12391, were downregulated in the OA group. Target genes of tsRNA-12391 mainly participated in mitophagy-related pathways such as Rap1 signaling pathway. Compared to the control group, tsRNA-12391 mimics significantly promoted mitophagy, as shown by the upregulated expression of PINK1 and LC3 and the co-localization of Mito-Tracker Green and PINK1. Furthermore, tsRNA-12391 mimics effectively enhanced chondrogenesis in chondrocytes, as demonstrated by the elevated expression of collagen II and ACAN. AMSC-exos with tsRNA-12391 overexpression also facilitated mitophagy and chondrogenesis in vitro and in vivo. Mechanistically, tsRNA-12391 bound to ATAD3A restricted ATAD31 from degrading PINK1, leading to PINK1 accumulation. ATAD31 overexpression reversed the effects of tsRNA-12391 mimics on mitophagy and chondrogenesis. AMSC-exos loaded with tsRNA-12391 promoted mitophagy and chondrogenesis by interacting with ATAD31; this may be a novel therapeutic strategy for OA.

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来源期刊
Biotechnology Journal
Biotechnology Journal Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
8.90
自引率
2.10%
发文量
123
审稿时长
1.5 months
期刊介绍: Biotechnology Journal (2019 Journal Citation Reports: 3.543) is fully comprehensive in its scope and publishes strictly peer-reviewed papers covering novel aspects and methods in all areas of biotechnology. Some issues are devoted to a special topic, providing the latest information on the most crucial areas of research and technological advances. In addition to these special issues, the journal welcomes unsolicited submissions for primary research articles, such as Research Articles, Rapid Communications and Biotech Methods. BTJ also welcomes proposals of Review Articles - please send in a brief outline of the article and the senior author''s CV to the editorial office. BTJ promotes a special emphasis on: Systems Biotechnology Synthetic Biology and Metabolic Engineering Nanobiotechnology and Biomaterials Tissue engineering, Regenerative Medicine and Stem cells Gene Editing, Gene therapy and Immunotherapy Omics technologies Industrial Biotechnology, Biopharmaceuticals and Biocatalysis Bioprocess engineering and Downstream processing Plant Biotechnology Biosafety, Biotech Ethics, Science Communication Methods and Advances.
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