{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:46:37Z","timestamp":1791877597339,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,10,12]],"date-time":"2014-10-12T00:00:00Z","timestamp":1413072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteoblastic differentiation and bone\u2010forming 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\u2010E1 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\u2010E1 cells cultured under hypoxic conditions. Melatonin upregulated ALP activity and <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of <jats:italic>Alp<\/jats:italic>,<jats:italic> Osx<\/jats:italic>,<jats:italic> Col1<\/jats:italic>, and <jats:italic>Ocn<\/jats:italic> in a time\u2010 and concentration\u2010dependent manner. Alizarin red S staining showed that the mineralized matrix in hypoxic MC3T3\u2010E1 cells formed in a manner that was dependent on melatonin concentration. Moreover, melatonin stimulated phosphorylation of p38 Mapk and Prkd1 in these MC3T3\u2010E1 cells. We concluded that melatonin promotes osteoblastic differentiation of MC3T3\u2010E1 cells under hypoxic conditions via the p38 Mapk and Prkd1 signaling pathways.<\/jats:p>","DOI":"10.1111\/jpi.12177","type":"journal-article","created":{"date-parts":[[2014,9,24]],"date-time":"2014-09-24T08:09:41Z","timestamp":1411546181000},"page":"385-392","source":"Crossref","is-referenced-by-count":64,"title":["Melatonin promotes osteoblast differentiation and mineralization of <scp>MC<\/scp>3T3\u2010E1 cells under hypoxic conditions through activation of <scp>PKD<\/scp>\/p38 pathways"],"prefix":"10.1111","volume":"57","author":[{"given":"Jang\u2010Ho","family":"Son","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Ulsan University Hospital College of Medicine Ulsan University Ulsan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeong\u2010Cheol","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Oral and 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