MiR-128 inhibits the osteogenic differentiation in osteoporosis by down-regulating SIRT6 expression. Issue 9 (24th September 2019)

• Record Type: Journal Article
• Authors: Zhao, Jindong; Liu, Shaohui; Zhang, Wenhui; Ni, Linying; Hu, Zhenming; Sheng, Zhigang; Yin, Bo
• Is Part Of: Bioscience reports. Volume 39:Issue 9(2019)
• Publication Date: 2019-09-24
• Subjects: miR-128 -- osteoblast differentiation -- osteoporosis -- SIRT6; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20191405
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : Background: MicroRNAs (miRNAs) are involved in the regulation of osteogenic differentiation and chondrification in vivo . The purpose of the present study was to explore the potential mechanism of miR-128 in osteoporosis (OP). Methods : Quantitative real-time PCR (qRT-PCR) was used to determine the expression of miR-128 in femoral neck trabecular bones of OP patients ( n =40) and non-OP patients ( n =40). C2C12 cells were transfected with miR-128 mimic or inhibitor to determine the effect of miR-128 on osteoblastic differentiation of C2C12 cells. Bioinformatics and luciferase reporter genes were used to determine the molecular mechanism of miR-128 in osteoblastic differentiation of C2C12 cells. Results : The qRT-PCR results showed that the expression level of miR-128 in bone samples of OP patients was significantly higher than that of non-OP patients, while miR-128 was significantly down-regulated during the osteogenic differentiation of C2C12 cells. In addition, the results showed that overexpression of miR-128 significantly inhibited the mRNA and protein expression levels of osteocalcin (OC), alkaline phosphatase (ALP) and collagen I type-α1 (COL1A1) in C2C12 cells, while miR-128 inhibitor could reverse this effect. Bioinformatics analysis and dual-luciferase reporter assay found that silencing information regulatory protein 6 (SIRT6) was a direct target of miR-128. The qRT-PCR and Western Blot results found that miR-128 significantly down-regulated the mRNA and protein expressions of SIRT6. Furthermore, silencing SIRT6 significantly inhibited the promoting effect of the miR-128 inhibitor on the expression of osteoblast markers. Conclusion : The above results confirmed that miR-128 inhibited osteoblast differentiation in OP by down-regulating SIRT6 expression, thus accelerating the development of OP.