MicroRNAs (miRNAs) are non-coding RNAs that are approximately 22 nucleotides in length. miRNAs play important roles in post-transcriptional regulation by interacting with the 3′ untranslated region (3′UTR) of target genes, which induces mRNA degradation or suppresses protein translation (Bartel, 2004; Mohr et al. , 2015; O’Brien et al. , 2018). A series of miRNAs have been characterized as regulators of osteogenic activity and osteoblastic bone formation, either positively or negatively, through multiple signaling pathways (Hata et al. , 2015; Vimalraj et al. , 2013; Zhang et al. , 2017). miRNAs plays a critical role in regulating the osteogenic differentiation of BMSCs (Li, 2018; Wang et al. , 2019). For example, miR-149-3p regulates the switch between adipogenic and osteogenic differentiation of BMSCs by targeting FTO (Li et al. , 2019). Moreover, miR-488 is a negative regulator of psoralen-induced osteogenic differentiation of BMSCs by targeting Runx2 (Huang et al. , 2019).
Carbon monoxide releasing molecules (CORMs) are newly identified transition metal carbonyl-based compounds, able to efficiently regulate the release of CO (Motterlini et al. , 2003). Previously, we have discovered that CORM-3 promoted the osteogenic differentiation of rat BMSCs (Li et al. , 2018), and the same result was acquired in the periodontal ligament cells (PDLCs) (unpublished data). However, the underlying molecular mechanism remains unclear. In the experiments of our research group, the gene sequencing result of CORM-3-stimulated PDLCs showed that miR-195-5p was significantly down-regulated during osteogenic differentiation. To date, the role of miRNAs in CORM-3-induced osteogenic differentiation is poorly understood. As miRNAs are highly conserved, we hypothesized that miR-195-5p might be a regulator of CORM-3-induced osteogenic differentiation of rat BMSCs. In the present study, the effects of miR-195-5p on CORM-3-induced osteogenic differentiation of rat BMSCs, and its regulatory pathway were investigated in vitro, which was aimed to provide insight into the mechanism underlying the beneficial effects of CORM-3 and to explore the new potential therapy approach for bone regeneration.