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Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation.

ABSTRACT: Osteoporosis and other manifestations of bone disease are frequent in patients with systemic mastocytosis (SM) in association with the presence of mast cell infiltrates in bone marrow, although the mechanisms behind bone disease remain poorly understood. We find that extracellular vesicles (EVs) released by neoplastic mast cells and present in the serum of patients with SM (SM-EVs) block osteoblast differentiation and mineralization in culture, and when injected into mice diminish the expression of osteoblast markers, and trabecular bone volume and microarchitecture. We demonstrate that miRNA-30a and miRNA-23a, increased in SM-EVs and neoplastic mast cell-derived EVs, attenuate osteoblast maturation by suppressing expression of RUNX2 and SMAD1/5, essential drivers of osteogenesis. Thus, SM-EVs carry and deliver miRNAs that epigenetically interfere with bone formation and can contribute to bone mass reduction in SM. These findings also suggest possibilities for novel approaches to the management of bone disease in mast cell proliferative disorders.

SUBMITTER: Kim DK

PROVIDER: S-EPMC8100305 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation.

Kim Do-Kyun DK Bandara Geethani G Cho Young-Eun YE Komarow Hirsh D HD Donahue Danielle R DR Karim Baktiar B Baek Moon-Chang MC Kim Ho Min HM Metcalfe Dean D DD Olivera Ana A

Nature communications 20210505 1

Osteoporosis and other manifestations of bone disease are frequent in patients with systemic mastocytosis (SM) in association with the presence of mast cell infiltrates in bone marrow, although the mechanisms behind bone disease remain poorly understood. We find that extracellular vesicles (EVs) released by neoplastic mast cells and present in the serum of patients with SM (SM-EVs) block osteoblast differentiation and mineralization in culture, and when injected into mice diminish the expression ...[more]

PMID: 33953168

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Project description:BackgroundSevere cases of COVID-19 are characterized by an excessive presence of neutrophils. Neutrophil extracellular traps (NETs), released by activated neutrophils due to SARS-CoV-2 infection, contribute to lung epithelial cell death and are key drivers in COVID-19-associated immunothrombosis. However, the mechanism underlying NET formation in COVID-19 remain unclear.MethodsExtracellular vesicles (EVs) were isolated from the serum of COVID-19 patients and healthy volunteers, while neutrophils were isolated from blood samples of healthy volunteers. Neutrophils were treated with EVs, and the formation of NETs was observed. To identify the components responsible for the COVID-19-EVs-induced NET formation, we analyzed the expression profiles of microRNA (miRNAs) in COVID-19-EVs. We identified eight highly expressed miRNAs in COVID-19-EVs and explored their potential roles in COVID-19-EVs-mediated NET formation. Additionally, we explored the role of miR-20b-5p in COVID-19-EVs-induced NET formation.ResultsIn this study, we demonstrate that patients with COVID-19 have a higher concentration of serum EVs (COVID-19-EVs) than healthy controls (Normal-EVs). We also found that COVID-19-EVs are internalized by neutrophils to induced NET formation. Through comprehensive miRNA profiling of COVID-19-EVs versus Normal-EVs, we identified 78 differentially expressed miRNAs, with 27 of these being upregulated and 51 being downregulated. Subsequently, we discovered that COVID-19-EVs that were highly abundant with certain miRNAs promote NET formation. Specifically, miR-20b-5p was found to be the strongest inducer of NET formation of the identified miRNAs. Inhibition of miR-20b-5p resulted in a significant decrease in COVID-19-EVs-mediated induction of NET formation.ConclusionHerein, we reveal a previously unknown role of COVID-19-EVs in NET formation, which contributes to COVID-19 progression. This study suggests that miR-20b-5p may serve as a potential therapeutic target for COVID-19 treatment.

Dataset Information

Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation.

Publications

Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation.

Similar Datasets

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