Effects of melatonin on adult human mesenchymal stem cells in osteoblastic differentiation

Among the numerous functions of melatonin, the control of survival and differentiation of mesenchymal stem cells (MSCs) has been recently proposed. MSCs are a heterogeneous population of multipotent elements resident in tissues such as bone marrow, muscle, and adipose tissue, which are primarily involved in developmental and regeneration processes, gaining thus increasing interest for tissue repair and restoration therapeutic protocols. Melatonin directly accelerated the differentiation of human stem cells into osteoblasts and also suggested that melatonin could be applied as a pharmaceutical agent to promote bone regeneration. Inflammatory cytokines and adipokines, proangiogenic/mitogenic stimuli, and other mediators that influence the differentiation processes may affect the survival and functional integrity of these mesenchymal precursor cells. In this scenario, melatonin seems to regulate signaling pathways that drive commitment and differentiation of MSC into osteogenic, chondrogenic, adipogenic, or myogenic lineages. Common pathways suggested to be involved as master regulators of these processes are the Wnt/β-catenin pathway, the mitogen-activated protein kinases and the, transforming growth factor-β signaling. In this respect, melatonin emerges a novel and potential modulator of MSC lineage commitment and adipogenic differentiation. This review recognizes and critically examines the available information on the effect of melatonin as a regulator of MSC differentiation and protection in different organs and tissues.