Melatonin Promotes Osteoblastic Differentiation of MC3T3-E1 Cells Under Hypoxic Condition

Jangho Son DDS, PhD, Oral and Maxillofacial Surgery, Ulsan University Hospital, College of Medicine,Ulsan University, Ulsan, South Korea
Yeong-Cheol Cho DDS, PhD, Ulsan University Hospital, College of Medicine, Ulsan University, Ulsan, South Korea
Iel-Yong Sung DDS, PhD, Ulsan University Hospital, College of Medicine, Ulsan University, Ulsan, South Korea
Dong-Yul Kim DDS, MS, Ulsan University Hospital, College of Medicine, Ulsan University, Ulsan, South Korea
Yong-Deok Kim DDS, PhD, School of Dentistry, Pusan National University, Yangsan, South Korea
Melatonin has been shown to influence cell differentiation, where it can either stimulate or suppress cell division depending on its concentration or the cell type examined. A number of in vitro and in vivo studies have suggested beneficial effect of melatonin on promotion of osteoblastic differentiation. However, its precise mechanisms and the signaling pathway involved in the process, especially under hypoxic conditions have remained unknown. This presented study was performed to determine whether melatonin could promote osteoblastic differentiation of mouse preosteoblastic MC3T3-E1 cells and their mineralization activities under hypoxic conditions. In addition, we examined the signaling mechanisms mediating the melatonin actions on this processes. The results demonstrate that melatonin is capable of promoting differentiation and mineralization of preosteoblastic MCT3-E1 cells grown under hypoxic cultured condition. mRNA gene expressions of ALP, Osx, Col-I, and OCN were enhanced with melatonin treatment in time-and concentration-dependent manners. Alizarin red S staining showed that mineralized matrix in hypoxic MC3T3-E1 cells was formed in a concentration-dependent manner. In this processes, melatonin stimulated phosphorylation of p38 MAPK and PDK in MC3T3-E1 cells. Overall, we concluded that melatonin promotes osteoblastic differentiation of MC3T3-E1 cells under hypoxic condition via p38 MAPK and PKD signaling pathway

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