MOTS-c accelerates bone fracture healing by stimulating osteogenesis of bone marrow mesenchymal stem cells via positively regulating FOXF1 to activate the TGF-ß pathway.
Eur Rev Med Pharmacol Sci
; 23(24): 10623-10630, 2019 Dec.
Article
em En
| MEDLINE
| ID: mdl-31858528
ABSTRACT
OBJECTIVE:
To elucidate the function of MOTS-c in accelerating bone fracture healing by inducing BMSCs differentiation into osteoblasts, as well as its potential mechanism. MATERIALS ANDMETHODS:
Primary BMSCs were extracted from rats and induced for osteogenesis. The highest dose of MOTS-c that did not affect BMSCs proliferation was determined by CCK-8 assay. After 7-day osteogenesis, the relative levels of ALP, Bglap, and Runx2 in MOTS-c-treated BMSCs influenced by FOXF1 were examined. ALP staining and alizarin red S staining in BMSCs were performed as well. The interaction between FOXF1 and TGF-ß was analyzed by ChIP assay. At last, rescue experiments were performed to uncover the role of FOXF1/TGF-ß axis in MOTS-c-induced osteogenesis.RESULTS:
1 µM MOTS-c was the highest dose that did not affect BMSCs proliferation. MOTS-c treatment upregulated the relative levels of ALP, Bglap, and Runx2, and stimulated mineralization ability in BMSCs, which were attenuated by the silence of FOXF1. TGF-ß was proved to interact with FOXF1, and its level was positively mediated by FOXF1. The silence of FOXF1 attenuated the accelerated osteogenesis and TGF-ß upregulation in BMSCs because of MOTS-c induction, and these trends were further reversed by the overexpression of TGF-ß.CONCLUSIONS:
MOTS-c treatment markedly induces osteogenesis in BMSCs. During MOTS-c-induced osteogenic progression, the upregulated FOXF1 triggers the activation of TGF-ß pathway, thus accelerating bone fracture healing.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Regulação da Expressão Gênica
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Fator de Crescimento Transformador beta
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Consolidação da Fratura
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Proteínas Mitocondriais
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Células-Tronco Mesenquimais
Limite:
Animals
Idioma:
En
Revista:
Eur Rev Med Pharmacol Sci
Assunto da revista:
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China