Muscone Promotes The Adipogenic Differentiation Of Human Gingival Mesenchymal Stem Cells By Inhibiting The Wnt/β-Catenin Signaling Pathway

Abstract

Wen-Xiu Yuan,1 Xu-Xia Wang,2 De-Hua Zheng,1 Dan Ma,1 Qun Cui,1 Fan Yang,1 Jun Zhang1 1Department of Orthodontics, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong Province, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Jun ZhangDepartment of Orthodontics, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration, No. 44-1 Wenhua Road West, Jinan, Shandong Province, People’s Republic of ChinaTel [phone]Email [email protected]: This study was performed to evaluate the effects of muscone on the proliferation, migration and differentiation of human gingival mesenchymal stem cells (GMSCs) and to explore the relevant mechanisms.Materials and methods: We performed studies to determine the effects and mechanisms of muscone on GMSC proliferation, migration and differentiation. We conducted CCK-8, colony formation, transwell chamber, scratch wound, alkaline phosphatase (ALP) staining and activity, and alizarin red and oil red O staining assays, as well as real-time quantitative polymerase chain reaction (qRT-PCR), to ascertain the effects of muscone on GMSC proliferation, migration and differentiation in vitro. The mechanism by which muscone influences the osteogenic and adipogenic differentiation of GMSCs was elucidated by qRT-PCR and Western blotting.Results: We found that muscone significantly promoted GMSC proliferation, chemotaxis, wound healing and fat droplet formation and inhibited ALP activity and mineral deposition. Notably, we observed that the Wnt/β-catenin pathway was closely related to the ability of muscone to inhibit the osteogenic differentiation and promote the adipogenic differentiation of GMSCs. The effect of muscone on the multidirectional differentiation capacity of GMSCs was significantly reversed by the agonist lithium chloride through the Wnt/β-catenin signaling pathway.Conclusion: Muscone effectively increased the proliferation and migration, promoted the adipogenic differentiation and inhibited the osteogenic differentiation of GMSCs by inhibiting the Wnt/β-catenin signaling pathway. These results may provide a theoretical basis for the application of GMSCs and muscone in tissue engineering and regenerative medicine.Keywords: muscone, gingival mesenchymal stem cells, GMSCs, differentiation, Wnt/β-catenin signaling pathway, proliferation, chemotaxis

Keywords

• Muscone；Gingival mesenchymal stem cells(GMSCs)； Differentiation；Wnt/β-catenin signaling pathway；Proliferation；Chemotaxis