miR-134 inhibits chondrogenic differentiation of bone marrow mesenchymal stem cells by targetting SMAD6

Abstract

Various of microRNAs (miRNAs) have been reported to regulate the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), however, whether miR-134 plays a role in this biological process remains undetermined. In this present study, we firstly evaluated the chondrogenic differentiation of BMSCs by Alcian blue staining, and examined the miR-134 expression by qRT-PCR during this process. And miR-134 inhibitor was used to investigate the functions of miR-134 in chondrogenic differentiation of BMSCs by Alcian blue staining, qRT-PCR and western blot. Subsequently, the correlation between miR-134 and SMAD6 was assessed via bioinformatics analysis and dual luciferase reporter assay. Finally, the roles of SMAD6 in chondrogenic differentiation of BMSCs was also determined through Alcian blue staining, qRT-PCR and western blot. As results showed that miR-134 expression was significantly downregulated during chondrogenic differentiation, and inhibition of miR-134 obviously promoted chondrogenic differentiation. Dual luciferase reporter assay indicated that miR-134 could directly targeted the 3'-UTR of SMAD6, inhibited miR-134 expression in BMSCs could upregulate SMAD6 expression. Moreover, we found that overexpression of SMAD6 significantly promoted chondrogenic differentiation, and this SMAD6 induced promotion of chondrogenic differentiation could be reversed by miR-134 mimics. In conclusion, our findings suggested that miR-134 may act as a negative regulator during chondrogenic differentiation of BMSCs by interacting with SMAD6.

Irisin enhances chondrogenic differentiation of human mesenchymal stem cells via Rap1/PI3K/AKT axis.

“…Accumulated evidences have shown that post-transcriptional regulation by microRNAs (miRNAs) was involved in the osteogenic and chondrogenic differentiation of MSCs [27,41] . It was a practical approach to mediate the chondrogenic differentiation of MSCs by manipulating the expression of speci c miRNAs [42][43][44] . A variety of miRNAs participated in the processes of irisin on osteogenic differentiation of MSCs, browning of white adipocytes, and anti-in ammation [19,[45][46] .…”

Effects of miRNAs, lncRNAs and circRNAs on osteoporosis as regulatory factors of bone homeostasis (Review)

“…Similarly, SMads are involved in the process of chondrogenesis. Recent findings have shown that miR-134 expression was downregulated during chondrogenesis and that mir-134, by interacting with SMad6, acted as a negative regulator during the chondrogenic differentiation of BMScs (34).…”

Genome-wide DNA methylation and multi-omics study of human chondrocyte ontogeny and an epigenetic clock analysis of adult chondrocytes

“…Besides, age-correlated CpGs losing methylation with age and the transcriptional profile for the associated genes has been shown in FigS2-3. We also examined the methylation status of all age-correlated CpG probes associated with microRNA (miRNA) genes (Fig S4), which are known to play an important role in chondrocytes during development [26][27][28][29] . The age-correlated CpGs for these miRNAs also gain methylation with age and show downregulation in adult chondrocytes as revealed by the miRNAsequencing data (Fig 1h-i, Table S2).…”