RESUMO
The article "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, by F.-B. Weng, L.-F. Zhu, J.-X. Zhou, Y. Shan, Z.-G. Tian, L.-W. Yang, published in Eur Rev Med Pharmacol Sci 2019; 23 (24): 10623-10630-DOI: 10.26355/eurrev_201912_19759-PMID: 31858528" has been withdrawn from the authors due to inaccuracies during the process of organizing the images. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19759.
RESUMO
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-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.
Assuntos
Consolidação da Fratura , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Proteínas Mitocondriais/farmacologia , Osteogênese/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Células Cultivadas , Regulação para Baixo , Consolidação da Fratura/genética , Consolidação da Fratura/imunologia , Regulação da Expressão Gênica/imunologia , Inativação Gênica , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/genética , Osteogênese/imunologia , Cultura Primária de Células , Ratos , Transdução de Sinais , Fator de Crescimento Transformador beta/genética , Regulação para CimaRESUMO
OBJECTIVE: The aim of this study was to investigate the role of microRNA-222 (miR-222) in osteosarcoma (OS), and to further explore the potential molecular mechanism. PATIENTS AND METHODS: We measured the level of miR-222 in OS tissues and cell lines using quantitative Real-time polymerase chain reaction. Synthesized miR-222 mimics or inhibitors were obtained to up-regulate or down-regulate the expression of miR-222 in U2OS or Saos2 cells. Cell counting kit-8 (CCK8) and colony formation assay were employed to detect the ability of cell proliferation, and transwell assay was used to confirm the ability of cell invasion. Furthermore, luciferase assay and Western blot were applied to verify the target of miR-222 in OS. RESULTS: The level of miR-222 in OS tumor tissue samples was significantly lower than that in normal group. Over-expression of miR-222 decreased cell proliferation and invasion in U2OS cells while knockdown of miR-222 promoted cell growth and metastasis in Saos2 cells. Furthermore, YWHAG was found to be a candidate target of miR-222 using several databases. Elevated level of miR-222 inhibited YWHAG expression while reduced miR-222 promoted YWHAG expression. Also, up-regulation of YWHAG restored the inhibiting effect of miR-222 mimics. CONCLUSIONS: We identified for the first time that the expression level of miR-222 was reduced in OS tissues as well as in OS cell lines. miR-222 could inhibit cell proliferation and invasion via down-regulating YWHAG. These data could provide a potential target for the biological treatment of OS.
