ArticlePeerJ2022
M1 macrophage-derived extracellular vesicle containing tsRNA-5006c promotes osteogenic differentiation of aortic valve interstitial cells through regulating mitophagy.
Article in PeerJ, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Review
- Bioprosthetic heart valve degeneration: new insights into structural remodeling and calcification.Frontiers in cardiovascular medicine · 2026Review
- CHAtRF Modulates Cardiac Hypertrophy via SRSF5-Dependent Regulation of Psmg4 Alternative Splicing.Research (Washington, D.C.) · 2026Article
- The Emerging Role of tRNA-Derived Small RNAs (tsRNAs) in Radiation-Induced Cardiovascular PathologyEndocrine, metabolic & immune disorders drug targets · 2026Review
- Emerging roles of tsRNAs in programmed cell death and disease therapeutics: challenges, opportunities, and future directions.Non-coding RNA research · 2025Review
- Targeting ANT1 to regulate PINK1/Parkin-mediated mitophagy is an effective treatment of trauma-induced tendon heterotopic ossification.Journal of orthopaedic translation · 2025Article
- The novel tRF-23 promotes osteogenic differentiation of hBMSCs and protects against bone loss in ovariectomized mice.Stem cell reports · 2025Article
- The Role of tRNA-Derived Small RNAs (tsRNAs) in Regulating Cell Death of Cardiovascular Diseases.Biology · 2025Review
- Macrophage-driven exosomes regulate the progression of cardiovascular disease.Frontiers in pharmacology · 2025Review
- tsRNA-5006c regulates hippocampal neurons ferroptosis to ameliorate perioperative neurocognitive disorders in aged male mice.3 Biotech · 2025Article
- tRNA-derived small RNAs (tsRNAs) in cardiovascular diseases: biogenesis, functions, and therapeutic targets.Frontiers in cardiovascular medicine · 2025Review
- Macrophages as key modulators of calcific aortic valve disease.Frontiers in cardiovascular medicine · 2025Review
- Insights into preclinical models of calcific aortic valve disease and their translational potential.Frontiers in cardiovascular medicine · 2025Review
- The role of macrophages in vascular calcification: strategies for diagnosis and treatment.Frontiers in immunology · 2025Review
- The function of tRNA-derived small RNAs in cardiovascular diseases.Molecular therapy. Nucleic acids · 2024Review
- M1 macrophage-derived oncostatin M induces osteogenic differentiation of ligamentum flavum cells through the JAK2/STAT3 pathway.JOR spine · 2024Article
- Emerging role of extracellular vesicles and exogenous stimuli in molecular mechanisms of peripheral nerve regeneration.Frontiers in cellular neuroscience · 2024Review
- Osteopontin/SPP1: a potential mediator between immune cells and vascular calcification.Frontiers in immunology · 2024Review
- Regulatory mechanism of macrophage polarization based on Hippo pathway.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Osteogenic differentiation of aortic valve interstitial cells (AVICs) plays a key role in the calcific aortic valve disease progression. Extracellular vesicles (EVs)-derived from M1-polarized macrophages (M1-EVs) orchestrated intercellular communication by delivering non-coding RNAs such as tRNA-derived small RNAs (tsRNAs) is crucial for cardiovascular disease. However, the role and mechanism of M1-EVs tsRNAs in osteogenic differentiation of AVICs remains largely unclear. Methods: M1-EVs and PBS treated-RAW 264.7 cell-derived EVs (NC-EVs) were incubated with AVICs and subjected to small RNA sequencing. Candidate tsRNA in M1-EVs was silenced to explore their effects on AVIC osteogenic differentiation and mitophagy. Results: DiI-labeled M1-EVs were internalized by AVICs, resulting in significantly increased calcium nodule formation and expression of osteogenesis-related genes in AVICs, including RUNX2, BMP2, osteopontin, and SPP1, compared with NC-EVs. Small RNA sequencing revealed that 17 tsRNAs were significantly up-regulated such as tsRNA-5006c, while 28 tsRNAs were significantly down-regulated in M1-EVs compared with NC-EVs. Intriguingly, tsRNA-5006c-deleted M1-EVs treatment significantly reduced calcium nodule formation and expression of osteogenesis-related genes in AVICs relative to control group. Moreover, target genes of tsRNA-5006c were mainly involved in autophagy-related signaling pathways, such as MAPK, Ras, Wnt, and Hippo signaling pathway. Hallmarks of mitophagy activation in AVICs including mitophagosome formation, TMRM fluorescence, expression of LC3-II, BINP3, and PGC1α, were significantly elevated in the M1-EVs group compared with NC-EVs group, whereas M1-EVs tsRNA-5006c inhibitor led to a significant reduction in these indicators. Conclusion: M1-EVs carried tsRNA-5006c regulates AVIC osteogenic differentiation from the perspective of mitophagy, and we provide a new target for the prevention and treatment of aortic valve calcification.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.