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periodontal ligament cells (PDLCs) (unpublished data).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.