Study on the Mechanism of miR-146a in Gingival Mesenchymal Stem Cells

This study aimed to investigate the molecular mechanisms of microRNA-146a (miR-146a) on gingival mesenchymal stem cells (MSCs). Gingival MSCs were isolated from the gingiva tissues of patients with periodontal disease to reveal the function of miR-146a in regulating osteoblast differentiation. miR-146a inhibits osteoblast differentiation by inhibiting phosphorylated cyclic-AMP response binding (CREB) protein translocation into the nucleus and ultimately attenuating runt-related transcription factor 2 (Runx2) expression. Furthermore, silencing miR-146a promotes the proliferation of gingival MSCs. Of note, targeted inhibition of miR-146a also inhibited LPS-induced inflammatory response and promoted the proliferation of gingival MSCs via CREB/Runx2 axis. MiR-146a is a key negative regulator of gingival MSCs proliferation and osteogenic differentiation, and targeting to reduce the miR-146a expression is essential for bone formation signaling. Therefore, we propose that miR-146a is a useful therapeutic target for the development of bone anabolic strategies.