Open AccessMicro RNA ‐31a‐5p from aging BMSC s links bone formation and resorption in the aged bone marrow microenvironment
Author(s) -
Xu Rongyao,
Shen Xiang,
Si Yameng,
Fu Yu,
Zhu Weiwen,
Xiao Tao,
Fu Zongyun,
Zhang Ping,
Cheng Jie,
Jiang Hongbing
Publication year - 2018
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12794
Subject(s) - bone marrow , stromal cell , microbiology and biotechnology , bone resorption , osteoblast , resorption , medicine , chemistry , biology , endocrinology , in vitro , biochemistry
The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of micro RNA ‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells ( BMSC s) from aged rats, and these BMSC s demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT ‐rich sequence‐binding protein 2 ( SATB 2) levels and the aging of BMSC s by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci ( SAHF ). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSC s‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.