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
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteogenesis
/
Gene Expression Regulation
/
Transforming Growth Factor beta
/
Fracture Healing
/
Mitochondrial Proteins
/
Mesenchymal Stem Cells
Limits:
Animals
Language:
En
Journal:
Eur Rev Med Pharmacol Sci
Journal subject:
FARMACOLOGIA
/
TOXICOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
China