Melatonin Promotes Osteoblast Differentiation and Bone Formation

Abstract

Prior studies have demonstrated that the pineal hormone, melatonin, can stimulate chloramphenicol acetyltransferase activity in Drosophila SL-3 cells transfected with a chloramphenicol acetyltransferase reporter construct containing the response element of rat bone sialoprotein (BSP). Based on these findings, studies were performed to determine whether melatonin could similarly modulate the expression of BSP in two cell lines, the MC3T3-E1(MC3T3) pre-osteoblast and rat osteoblast-like osteosarcoma 17/2.8 cell. Initial studies demonstrated that MC3T3 cells grown in the presence of 50 nM melatonin underwent cell differentiation and mineralization by day 12 instead of the 21-day period normally required for cells grown in untreated media. Melatonin increased gene expression of BSP and the other bone marker proteins, including alkaline phosphatase (ALP); osteopontin; secreted protein, acidic and rich in cysteine; and osteocalcin in MC3T3 cells in a concentrationdependent manner. Levels of melatonin as low as 10 nM were capable of stimulating transcription of these genes when cells were grown in the presence of ␤-glycerophosphate and ascorbic acid. Under these conditions, melatonin induced gene expression of the bone marker proteins; however, this does not occur until the 5th day after seeding the culture dishes. Thereafter, MC3T3 cells responded to melatonin within 2 h of treatment. The fully differentiated rat osteoblast-like osteosarcoma 17/ 2.8 cells responded rapidly to melatonin and displayed an increase in the expression of BSP, ALP, and osteocalcin genes within 1 h of exposure to the hormone. To determine whether melatonin-induced osteoblast differentiation and bone formation are mediated via the transmembrane receptor, MC3T3 cells were treated in the presence and absence of melatonin with either luzindole, a competitive inhibitor of the binding of melatonin to the transmembrane receptors, or pertussis toxin, an uncoupler of G i from adenylate cyclase. Both luzindole and pertussis toxin were shown to reduce melatonin-induced expression of BSP and ALP. These results demonstrate, for the first time, that the pineal hormone, melatonin, is capable of promoting osteoblast differentiation and mineralization of matrix in culture and suggest that this hormone may play an essential role in regulating bone growth.Melatonin is the major hormone released from the pineal gland, and its levels are synchronized by environmental light with nightly plasma concentrations reaching approximately 50 times higher than that reached during daytime (1-3). Melatonin regulates a variety of physiological and pathophysiological processes including hypothalamic control of circadian rhythms (4 -6), regulation of reproductive function in seasonally breeding species (7), and regulation of temperature (8), sexual development (9, 10), the immune system (11), and the cardiovasculature (12). It has also been shown to influence cell differentiation where it can either stimulate or suppress cell division depending on its concentration or the cell ...

Effect of melatonin on osseointegration of immediate loading implant supported mandibular over denture: Randomized clinical trail

“…[14] Melatonin increases pre-osteoblast/osteoblast/osteoblastlike cell proliferation, promotes the expression of type I collagen and bone marker proteins interthread bone is an intermediate situation of new bone in with the implant by stimulation of osteoblasts and the old bone in the total peri implant area by osteoclast inhibition, and melatonin continues its activity passing on from the 2 nd to the 5 th week and to the 8 th week. [14][15][16] Arat Bilhan et al (2015) they said that use of a splinted attachment can be preferred to reduce forces emerging around the implants. The use of 2 solitary attachments in cases with good bone quality and ideal sized implants are safe with the bilateral loading on over dentures.…”

Bone Tissue Remodeling After the Introduction of Exogenous Melatonin in Different Seasons

“…Однак дані щодо його дії на ремо-делювання КТ нині є дискусійними. Серед головних ефектів цього гормону на КТ від-значають: стимуляцію диференціації та ак-тивації остеобластів, гальмування диферен-ціації остеокластів, нейтралізацію утворених остеокластами вільних радикалів, посилення синтезу колагенових і неколагенових білків кісткового матриксу [7][8][9]. Тобто встановле-на можливість циркадіанної інтенсивності фізіологічної регенерації КТ за допомогою зміни амплітуди та ритму добових флукту-ацій концентрації мелатоніну в організмі.…”

Effects of the Dichloromethane Fraction of Dipsaci Radix on the Osteoblastic Differentiation of Human Alveolar Bone Marrow-Derived Mesenchymal Stem Cells

“…It is used as a marker of bone formation during inorganic mineral deposition. 17,18) ALP is a marker activated during the early stages of osteoblast differentiation, whereas BSP and OC are expressed during the intermediate and late stages of differentiation.…”