MOTS-c accelerates bone fracture healing by stimulating osteogenesis of bone marrow mesenchymal stem cells via positively regulating FOXF1 to activate the TGF-β pathway
Authors: L-W Yang
J-X Zhou
Z-G Tian
Y Shan
F-B Weng
L-F Zhu
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MOTS-c; bone fracture healing; BMSCs; osteoblasts; osteogenesis
Affiliations: Department of Orthopedics, The Ninth People's Hospital of Suzhou, Suzhou, China. .

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 and methods: 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-β was analyzed by ChIP assay. At last, rescue experiments were performed to uncover the role of FOXF1/TGF-β 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-β was proved to interact with FOXF1, and its level was positively mediated by FOXF1. The silence of FOXF1 attenuated the accelerated osteogenesis and TGF-β upregulation in BMSCs because of MOTS-c induction, and these trends were further reversed by the overexpression of TGF-β. Conclusions: MOTS-c treatment markedly induces osteogenesis in BMSCs. During MOTS-c-induced osteogenic progression, the upregulated FOXF1 triggers the activation of TGF-β pathway, thus accelerating bone fracture healing. 

Retracted: Yes

PubPeer comments:
 Below three parts copied from the commented article can be seen. Figure 1 clearly shows that a 4000 member DNA encoded combinatorial library is synthesized by using the split and pool method of Furka et al. Furka, u00c1., Sebestyu00e9n, F., Asgedom, M., Dibu00f3, G. CORNUCOPIA OF PEPTIDES BY SYNTHESIS (1988) . In Highlights of Modern Biochemistry, Proceedings of the 14th International Congress of Biochemistry, Vol. 5, p. 47, VSP.Utrecht. Furka u00c1., Sebestyu00e9n F., Asgedom M., Dibu00f3 G. General method for rapid synthesis of multicomponent peptide mixtures Int. J. Peptide Protein Res. 37, 1991, 487-493. The Split and Pool Technology is executed in a series of cycles. Each cycle comprises three operations: 1.tSplitting the mixture of compounds into equal portions 2.tCoupling a building block (BB) to each portion 3.tMixing the portions In the synthesis of DNA encoded libraries a modification occurs in operation 2. An additional coupling is executed with a DNA oligomer encoding the BB. It is clear that the use of the split and pool method in DNA encoding is unavoidable and so citation of the method is normally inevitable. In this paper however, only the DNA encoding part is cited in Ref. 1. Citation of the split and pool method is completely omitted. The proper citations are replaced in Ref. 2-4 by mostly irrelevant publications. ![file] ![file] ![file] ,