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

Nat Commun. 2021 May 5;12(1):2527. doi: 10.1038/s41467-021-22754-4.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Calcification, Physiologic / physiology
  • Cell Differentiation
  • Cell Line
  • Child
  • Child, Preschool
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Extracellular Vesicles / metabolism*
  • Female
  • Humans
  • Male
  • Mast Cells / metabolism
  • Mastocytosis / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Middle Aged
  • Myeloproliferative Disorders / metabolism
  • Osteoblasts / metabolism*
  • Osteogenesis / physiology*
  • Smad1 Protein / metabolism
  • Smad5 Protein / metabolism
  • Young Adult


  • Core Binding Factor Alpha 1 Subunit
  • MIRN23a microRNA, human
  • MIRN30a microRNA, mouse
  • MIRN30b microRNA, human
  • MicroRNAs
  • Mirn23b microRNA, mouse
  • RUNX2 protein, human
  • Smad1 Protein
  • Smad5 Protein