Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo

Abstract

Melatonin is known to regulate a variety of physiological processes including control of circadian rhythms, regulation of seasonal reproductive function, regulation of body temperature, and so forth. Accumulating evidence from in vitro and in vivo experiments using rodent and chicken has also suggested that melatonin may have an influence on skeletal growth and bone formation. However, little is known about the effects of melatonin on human osteoblasts, which thus remains to be elucidated. This study was performed to determine whether melatonin could affect the proliferation and differentiation of human osteoblasts in vitro and to demonstrate the possibility that melatonin could be applied as a pharmaceutical agent to shorten the treatment period of bone fracture, various osteotomies, and bone distraction. Reverse transcription-polymerase chain reaction and Western blot analysis showed that human osteoblasts expressed melatonin 1a receptor and that its expression levels decreased gradually with the age of the hosts. Melatonin stimulated the proliferation and alkaline phosphatase activity of human osteoblasts in a dose-dependent manner at the pharmacological concentrations. Melatonin also promotes gene expression of type I collagen, osteopontin, bone sialoprotein, and osteocalcin in a dose-dependent manner, and stimulated the mineralized matrix formation in vitro. Moreover, intraperitoneal administration of melatonin to mice increased the volume of newly formed cortical bone of femora. These results demonstrated that melatonin directly accelerated the differentiation of osteoblasts of human as well as rodent and chicken and also suggested that melatonin could be applied as a pharmaceutical agent to promote bone regeneration.

Remodeling of the Bone Tissue of Rats of Different Lines After Melatonin Effect

“…But in both lines the growth had one direction. The received results are agreed with literary data as to the influence of melatonin on BT formation of young animals [6,15].…”

“…There are also other hypotheses as to melatonin influence on these processes. The dependence between the high concentration of melatonin in blood plasma of ratsmales of Wistar line and low level of markers of bone tissue formation was shown [4]. In other study the effects of melatonin impact on osteoblasts culture at presence of osteoclasts were analyzed.…”

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

“…Melatonin is believed to promote bone mass by increasing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts [54], promoting osteoblast proliferation [40] and reducing osteoblast RANKL expression [28]. In animal models of idiopathic scoliosis, such as the chick experimental pinealectomy model, the development of idiopathic scoliosis-like changes has been associated with reduced levels of serum melatonin.…”

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

“…Ці результати узгоджуються з літера тур ними даними щодо впливу мела тоніну у фармако-логічних дозах на проліферацію остеобластів та активність ЛФ [9,17]. Весною, навпаки, спостерігали лише зворотну тенденцію до зниження активності ЛФ на 8% порівняно з контрольними значеннями (рис.1).…”