Melatonin promotes osteoblastic differentiation through the BMP/ERK/Wnt signaling pathways

Department of Orthodondritics, Kyung-Hee University College of Dental Medicine, Seoul, Korea.
Journal of Pineal Research (Impact Factor: 9.6). 03/2011; 51(2):187-94. DOI: 10.1111/j.1600-079X.2011.00875.x
Source: PubMed


Although melatonin has a variety of biological actions such as antitumor, antiangiogenic, and antioxidant activities, the osteogenic mechanism of melatonin still remains unclear. Thus, in the present study, the molecular mechanism of melatonin was elucidated in the differentiation of mouse osteoblastic MC3T3-E1 cells. Melatonin enhanced osteoblastic differentiation and mineralization compared to untreated controls in preosteoblastic MC3T3-E1 cells. Also, melatonin increased wound healing and dose-dependently activated osteogenesis markers such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN), bone morphogenic protein (BMP)-2 and -4 in MC3T3-E1 cells. Of note, melatonin activated Wnt 5 α/β, β-catenin and the phosphorylation of c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in a time-dependent manner while it attenuated phosphorylation of glycogen synthase kinase 3 beta (GSK-3β) in MC3T3-E1 cells. Consistently, confocal microscope observation revealed that BMP inhibitor Noggin blocked melatonin-induced nuclear localization of β-catenin. Furthermore, Western blotting showed that Noggin reversed activation of β-catenin and Wnt5 α/β and suppression of GSK-3β induced by melatonin in MC3T3-E1 cells, which was similarly induced by ERK inhibitor PD98059. Overall, these findings demonstrate that melatonin promotes osteoblastic differentiation and mineralization in MC3T3-E1 cells via the BMP/ERK/Wnt pathways.

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    • "Study found that melatonin could inhibit tau hyperphosphorylation induced by inhibiting PI3K pathway (Deng et al. 2005) suggesting that melatonin maybe regulates the PI3K/Akt pathway. Subsequent studies have also demonstrated that melatonin is involved in regulating PI3K/Akt/GSK3 pathway (Hoppe et al. 2010; Park et al. 2011; Wang et al. 2012). "
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    Journal of Molecular Neuroscience 12/2014; 56(1). DOI:10.1007/s12031-014-0475-4 · 2.34 Impact Factor
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    • "It protects neurons from disorders associated with misfolded proteins (Jeong and Park, 2013). Melatonin has been reported to activate beta-catenin in osteoblastic cells (Park et al., 2011) and to increase beta-catenin levels in the brain of aged mice (Gutierrez-Cuesta et al., 2008), but to decrease beta-catenin levels in breast cancer cells (Mao et al., 2012). "
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    Life Sciences 09/2014; 115(1-2). DOI:10.1016/j.lfs.2014.08.024 · 2.70 Impact Factor
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    • "Melatonin, an indoleamine secreted by the pineal gland in a circadian manner, is a noteworthy free radical scavenger (12) and also plays an immunomodulatory role (13). Several studies have shown that melatonin stimulates the proliferation and synthesis of type I collagen and promotes bone formation (14,15). Melatonin may have implications in diseases of the oral cavity, limiting tissue damage that is a result of free radicals, stimulating the immune response and reducing the progressive loss of alveolar bone (16,17). "
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