Biological Effects of Melatonin on Osteoblast/Osteoclast Co ‐cultures, Bone and Quality of Life: implications of a role for MT2 melatonin receptors, MEK1/2 and MEK5 in melatonin‐mediated osteoblastogenesis

This study examines mechanisms related to the ratios of osteoblasts and osteoclasts using co‐culture models (transwell or layered) of human mesenchymal stem cell (MSCs) and human peripheral blood monocytes (PBMCs). Human MSCs/PBMCs co‐cultures exposed to melatonin in osteogenic (OS+) medium for 21 days induced osteoblast differentiation and mineralization; however, only in layered co‐cultures did melatonin inhibit osteoclastogenesis. Melatonin effects were mediated through MT2 melatonin receptors, MEK1/2 and MEK5. In layered but not transwell co‐cultures, melatonin increased OPG:RANKL ratios by inhibiting RANKL, suggesting that contact with osteoclasts during osteoblastogenesis inhibits RANKL secretion. Melatonin modulated expression of ERK1/2, ERK5, β1 integrin, GLUT4 and IRβ expression that was dependent upon the type of co‐culture; however, in both cultures, melatonin increased RUNX2 and decreased PPARγ expression, indicating a role for metabolic processes that control osteogenic versus adipogenic cell fates of MSCs. Furthermore, melatonin also has osteoblast‐inducing effects on human adipose‐derived MSCs. In vivo, one‐year nightly melatonin (15mg/L) given to neu female mice in their drinking water, increased pErk1/2, pErk5, Runx2 and Opg and Rankl levels in bone consistent with melatonin's already reported bone‐enhancing effects. Finally, analysis of daily logs from the MOPS demonstrated a significant improvement in mood and perhaps sleep quality in w...
Source: Journal of Pineal Research - Category: Research Authors: Tags: Original Article Source Type: research