title: Melatonin promotes osteoblast differentiation and mineralization of MC3T3-E1 cells under hypoxic conditions through activation of PKD/p38 pathways.
abstract: Osteoblastic differentiation and bone-forming capacity are known to be suppressed under hypoxic conditions. Melatonin has been shown to influence cell differentiation. A number of in vitro and in vivo studies have suggested that melatonin also has an anabolic effect on bone, by promoting osteoblastic differentiation. However, the precise mechanisms and the signaling pathways involved in this process, particularly under hypoxic conditions, are unknown. This study investigated whether melatonin could promote osteoblastic differentiation and mineralization of preosteoblastic MC3T3-E1 cells under hypoxic conditions. Additionally, we examined the molecular signaling pathways by which melatonin mediates this process. We found that melatonin is capable of promoting differentiation and mineralization of MC3T3-E1 cells cultured under hypoxic conditions. Melatonin upregulated ALP activity and mRNA levels of Alp, Osx, Col1, and Ocn in a time- and concentration-dependent manner. Alizarin red S staining showed that the mineralized matrix in hypoxic MC3T3-E1 cells formed in a manner that was dependent on melatonin concentration. Moreover, melatonin stimulated phosphorylation of p38 Mapk and Prkd1 in these MC3T3-E1 cells. We concluded that melatonin promotes osteoblastic differentiation of MC3T3-E1 cells under hypoxic conditions via the p38 Mapk and Prkd1 signaling pathways.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ulsan University Hospital, College of Medicine, Ulsan University, Ulsan, South Korea.
authors.forename: Jang-Ho
authors.initials: JH
authors.lastname: Son
authors.forename: Yeong-Cheol
authors.initials: YC
authors.lastname: Cho
authors.forename: Iel-Yong
authors.initials: IY
authors.lastname: Sung
authors.forename: In-Ryoung
authors.initials: IR
authors.lastname: Kim
authors.forename: Bong-Soo
authors.initials: BS
authors.lastname: Park
authors.forename: Yong-Deok
authors.initials: YD
authors.lastname: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002113:Calcification, Physiologic / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000975:Antioxidants; C089212:protein kinase D; D011493:Protein Kinase C; D008550:Melatonin
keywords: bone metabolism; hypoxia; pineal gland; signaling pathway