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

Author

Listed:
  • Do-Kyun Kim

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH)
    Institute for Basic Science (IBS)
    Jeonbuk National University)

  • Geethani Bandara

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH))

  • Young-Eun Cho

    (National Institute on Alcohol Abuse and Alcoholism, NIH
    Andong National University)

  • Hirsh D. Komarow

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH))

  • Danielle R. Donahue

    (National Institute of Neurological Disorders and Stroke, NIH)

  • Baktiar Karim

    (National Cancer Institute, NIH)

  • Moon-Chang Baek

    (Kyungpook National University)

  • Ho Min Kim

    (Institute for Basic Science (IBS))

  • Dean D. Metcalfe

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH))

  • Ana Olivera

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH))

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.

Suggested Citation

  • Do-Kyun Kim & Geethani Bandara & Young-Eun Cho & Hirsh D. Komarow & Danielle R. Donahue & Baktiar Karim & Moon-Chang Baek & Ho Min Kim & Dean D. Metcalfe & Ana Olivera, 2021. "Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22754-4
    DOI: 10.1038/s41467-021-22754-4
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