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Extracellular microRNA in age‐related bone loss
Author(s) -
Hamrick Mark
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.11.1
Subject(s) - microvesicles , microvesicle , microbiology and biotechnology , mesenchymal stem cell , extracellular vesicle , microrna , stromal cell , exosome , bone marrow , stem cell , extracellular vesicles , biology , chemistry , cancer research , immunology , biochemistry , gene
Microvesicle‐ and exosome‐mediated transport of microRNAs (miRNAs) represents a novel cellular and molecular pathway for cell‐cell communication, and previous studies have indicated that specific circulating extracellular microRNAs are associated with osteoporosis and bone fracture. We have investigated the hypothesis that extracellular vesicles (EVs), including exosomes and microvesicles, may contribute to bone loss with aging by transporting specific miRNAs. EVs isolated from bone marrow of aged mice are readily endocytosed by bone marrow stromal (stem) mesenchymal stem cells (BMSCs). Moreover, EVs from aged mice suppress the osteogenic differentiation of BMSCs. We then examined age‐related changes in the miRNAs carried by bone‐derived EVs. These data indicate that the miR‐183 cluster (miR‐183/‐182/‐96) is elevated with age in bone‐derived EVs isolated from different strains of aged mice. In silico analysis reveals that miR‐183 targets Hmox1, and reduced Hmox1 with miR‐183 transfection has previously been shown to increase osteoclastogenesis. We found that miR‐183 can also induce senescence and suppress the osteogenic differentiation of BMSCs, and others have demonstrated that miR‐182 can inhibit the osteogenic differentiation of BMSCs and MC3T3 osteoprogenitor cells. Together these data indicate that aging can significantly alter the miRNA cargo of extracellular vesicles in the bone marrow microenvironment, which may in turn contribute to age‐related bone loss. Support or Funding Information National Institute on Aging (NIA AG036675)