AUTHOR=Cheng Bin-Feng , Feng Xiao , Gao Yao-Xin , Jian Shao-Qin , Liu Shi-Rao , Wang Mian , Xie Yun-Fei , Wang Lei , Feng Zhi-Wei , Yang Hai-Jie TITLE=Neural Cell Adhesion Molecule Regulates Osteoblastic Differentiation Through Wnt/β-Catenin and PI3K-Akt Signaling Pathways in MC3T3-E1 Cells JOURNAL=Frontiers in Endocrinology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.657953 DOI=10.3389/fendo.2021.657953 ISSN=1664-2392 ABSTRACT=

Neural cell adhesion molecule (NCAM) is involved in cell multi-directional differentiation, but its role in osteoblast differentiation is still poorly understood. In the present study, we investigated whether and how NCAM regulates osteoblastic differentiation. We found that NCAM silencing inhibited osteoblast differentiation in pre-osteoblastic MC3T3-E1 cells. The function of NCAM was further confirmed in NCAM-deficient mesenchymal stem cells (MSCs), which also had a phenotype with reduced osteoblastic potential. Moreover, NCAM silencing induced decrease of Wnt/β-catenin and Akt activation. The Wnt inhibitor blocked osteoblast differentiation, and the Wnt activator recovered osteoblast differentiation in NCAM-silenced MC3T3-E1 cells. We lastly demonstrated that osteoblast differentiation of MC3T3-E1 cells was inhibited by the PI3K-Akt inhibitor. In conclusion, these results demonstrate that NCAM silencing inhibited osteoblastic differentiation through inactivation of Wnt/β-catenin and PI3K-Akt signaling pathways.