MiR-9-3 promotes osteoblast differentiation of bone marrow mesenchymal stem cells by targeting Smoc2
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ABSTRACT: MicroRNAs are critical regulators of osteoblast differentiation and bone formation. In this study, we reported that miR-9-3 regulate osteoblast differentiation and bone formation by targeting SPARC-related modular calcium binding 2 (Smoc2). MiR-9-3 deletion led to reduced size and postweaning lethality in 10% of the mice. Using microcomputed tomography, we found that mice lacking miR-9-3 exhibited decreased trabecular bone mass and bone volume. Importantly, the serum level of PINP and OCN, both markers of bone formation, was also significantly decreased in miR-9-3-deficient mice. Deletion of miR-9-3 in mice did not affect osteoclast differentiation but impaired mesenchymal stem cells (MSCs)-mediated osteoblast differentiation and mineralization, as evidenced by reduced ALP and Alizarin Red S staining. RNA sequencing revealed reduced osteoblast differentiation and bone morphogenetic proteins (BMPs) signaling in miR-9-3-deficient MSCs. Mechanistically, dual-luciferase reporter assays identified Smoc2, an antagonist of BMP, as the direct target of miR-9-3. Moreover, miR-9-3 deficiency led to Smoc2 upregulation, which subsequently inhibited BMP/Smad pathway in MSCs. Collectively, our results reveal that Smoc2, a repressor of BMP signaling, is directly targeted and suppressed by miR-9-3, and loss of miR-9-3 increases Smoc2 expression, thereby reducing BMP signaling and impairing osteoblast differentiation.
ORGANISM(S): Mus musculus
PROVIDER: GSE345456 | GEO | 2026/09/03
REPOSITORIES: GEO
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