Biological Functions of Let-7e-5p in Promoting the Differentiation of MC3T3-E1 Cells

Abstract

MicroRNAs let-7c and let-7f, two members of the let-7 family, were involved in regulating osteoblast differentiation and have an important role in bone formation. Let-7e-5p, which also belonged to the let-7 family, presented in the differentiation of adipose-derived stem cells and mouse embryonic stem cells. However, the role of let-7e-5p in osteoblast differentiation was unclear. Thus, this study aimed to elucidate the function of let-7e-5p in osteoblast differentiation and its mechanism. Firstly, we found that the let-7e-5p mimic promoted osteoblast differentiation but not the proliferation of MC3T3-E1 cells by positively regulating the expression levels of osteogenic-associated genes (RUNX2, OCN, OPN, and OSX), the activity of ALP, and formation of mineralized nodules. Moreover, we ascertained that the let-7e-5p mimic downregulated the post-transcriptional expression of SOCS1 by specifically binding to the 3′ untranslated region of SOCS1 mRNA. Also, let-7e-5p-induced SOCS1 downregulation increased the protein levels of p-STAT5 and IGF-1, which were both modulated by SOCS1 molecules. Furthermore, let-7e-5p abrogated the inhibition of osteogenic differentiation mediated by SOCS1 overexpression. Therefore, these results suggested that let-7e-5p regulated the differentiation of MC3T3-E1 cells through the JAK2/STAT5 pathway to upregulate IGF-1 gene expression by inhibiting SOCS1. These findings may provide a new insight into the regulatory role of let-7e-5p in osteogenic differentiation and imply the existence of a novel mechanism underlying let-7e-5p-mediated osteogenic differentiation.

Genetically engineered M2-like macrophage-derived exosomes for P. gingivalis-suppressed cementum regeneration: From mechanism to therapy

“…In consistent with the studies, we also observed increased expression of Let-7d-5p , Let-7f-5p , Let-7i-5p in Ckip-1 silencing-induced M2 macrophages. Moreover, relevant studies have also shown that several subtypes, including Let-7f-5p , Let-7i-5p could promote osteoblast mineralization, the osteogenic differentiation of stem cells, and bone formation [ 34 , [38] , [39] , [40] ]. Further, the enhanced osteogenic differentiation was partially attributed to the delivered Let-7 miRNAs in exosomes [ 41 ], suggesting the possibility of exosomal transfer of Let-7 miRNAs from Ckip-1-silenced macrophages to cementoblasts.…”

Osteogenic Differentiation Effect of Human Periodontal Ligament Stem-Cell Initial Cell Density on Autologous Cells and Human Bone Marrow Stromal Cells

“…The role of osterix is to induce the differentiation of osteoprogenitors into pre-osteoblasts. The osterix pathway affects the expression of OCN, which indicates that pre-osteoblasts have already differentiated into osteoblasts [ 39 ]. The previous report also indicated the differentiation of osteoblasts through the upregulation of RUNX2 and the role of osterix as an inducer.…”

Genetic variation within the pri-let-7f-2 in the X chromosome predicting stroke risk in a Chinese Han population from Liaoning, China: From a case-control study to a new predictive nomogram

“…Since the A allele could be a risk factor for IS, individuals with the AA genotype may have a higher risk of developing IS. Studies have linked the let-7f genes with tumor cell growth, migration, and differentiation (28,29). Therefore, previous studies focused on the role of the rs17276588 polymorphism in the development Clinical and demographic ischemic stroke (IS) risk factors in the female population according to the least absolute shrinkage and selection operator (LASSO) binary logistic regression model.…”

“…Since the A allele could be a risk factor for IS, individuals with the AA genotype may have a higher risk of developing IS. Studies have linked the let-7f genes with tumor cell growth, migration, and differentiation ( 28 , 29 ). Therefore, previous studies focused on the role of the rs17276588 polymorphism in the development of various cancers ( 30 ).…”