title: Melatonin regulates mesenchymal stem cell differentiation: a review.
abstract: 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. Receptor-dependent and receptor-independent responses to melatonin are suggested to occur in these cells. These involve antioxidant or redox-dependent functions of this indolamine as well as secondary effects resulting from autocrine and paracrine responses. 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 MAPKs and the, TGF-β signaling. In this respect melatonin emerges a novel and potential modulator of MSC lineage commitment and adipogenic differentiation. These and other aspects of the physiological and pharmacological effects of melatonin as regulator of MSC are discussed in this review.
authors.affiliation: Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Luchetti
authors.forename: Barbara
authors.initials: B
authors.lastname: Canonico
authors.forename: Desirée
authors.initials: D
authors.lastname: Bartolini
authors.forename: Marcella
authors.initials: M
authors.lastname: Arcangeletti
authors.forename: Silvia
authors.initials: S
authors.lastname: Ciffolilli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Murdolo
authors.forename: Marta
authors.initials: M
authors.lastname: Piroddi
authors.forename: Stefano
authors.initials: S
authors.lastname: Papa
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: Francesco
authors.initials: F
authors.lastname: Galli
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D054392:Adipokines / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008550:Melatonin / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D054392:Adipokines; D000975:Antioxidants; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D008550:Melatonin
keywords: PPRAγ; Wnt; adipogenesis; differentiation; melatonin; mesenchymal stem cells; osteogenesis; oxidative stress; proliferation