MicroRNA let‐7c‐5p promotes osteogenic differentiation of dental pulp stem cells by inhibiting lipopolysaccharide‐induced inflammation via HMGA2/PI3K/Akt signal blockade

• Published in: Clinical and experimental pharmacology & physiology Vol. 46; no. 4; pp. 389 - 397
• Main Authors: Yuan, Hao, Zhao, Hongyan, Wang, Jiafeng, Zhang, Hong, Hong, Lihua, Li, He, Che, Hongze, Zhang, Zhimin
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.04.2019
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Alkaline phosphatase; Animal models; Biocompatibility; Bone growth; Calcium; Cbfa-1 protein; Cell growth; Cell proliferation; Dental pulp; dental pulp stem cell; Differentiation (biology); HMGA2; Inflammation; let‐7c‐5p; Lipopolysaccharides; miRNA; Msx2 protein; Osteogenesis; Ribonucleic acid; RNA; Signal transduction; Signaling; Stem cell transplantation; Stem cells; HMGA2; dental pulp stem cell; osteogenesis; inflammation; let-7c-5p
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.13059

Summary Pulpitis suppressed the level of let‐7c‐5p that promotes osteogenesis and bone formation by repressing HMGA2. In the current study, the function of let‐7c‐5p in the inflammation and osteogenesis in dental pulp stem cells (DPSCs) was explored. The level of let‐7c‐5p in DPSCs was up‐regulated, and the cells were subjected to lipopolysaccharide (LPS) to induce inflammation. The effect of let‐7c‐5p on cell proliferation potential, osteogenic differentiation potential, and activity of HMGA2/PI3K/Akt pathway was detected. The administration of LPS suppressed the cell proliferation of DPSCs and suppressed calcium deposition, activity of alkaline phosphatase (ALP), and levels of OCN, OPN, OSX, MSX2, and RUNX2 in inflamed DPSCs. The impaired osteogenic differentiation of inflamed DPSCs was associated with the increased levels of HMGA2, p‐PI3K, and p‐Akt. In let‐7c‐5p‐overexpressed inflamed DPSCs, the proliferation and osteogenic differentiation potential of DPSCs were restored, and the activation of HMGA2/PI3K/Akt signalling was inhibited. In rat pulpitis models, the injection of let‐7c‐5p agomir restored the osteogenic differentiation potential of dental pulp cells and inhibited HMGA2/PI3K/Akt signalling. The findings demonstrated the anti‐inflammation and pro‐osteogenesis effect of let‐7c‐5p during the attack of pulpitis, which depended on the inhibition of HMGA2/PI3K/Akt signalling.