Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation.
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
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 05 2021
05 05 2021
Historique:
received:
23
05
2019
accepted:
11
03
2021
entrez:
6
5
2021
pubmed:
7
5
2021
medline:
25
5
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33953168
doi: 10.1038/s41467-021-22754-4
pii: 10.1038/s41467-021-22754-4
pmc: PMC8100305
doi:
Substances chimiques
Core Binding Factor Alpha 1 Subunit
0
MIRN23a microRNA, human
0
MIRN30a microRNA, mouse
0
MIRN30b microRNA, human
0
MicroRNAs
0
Mirn23b microRNA, mouse
0
RUNX2 protein, human
0
Smad1 Protein
0
Smad5 Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2527Subventions
Organisme : Intramural NIH HHS
ID : ZIA AI001206
Pays : United States
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