The role of melatonin in bone regeneration: A review of involved signaling pathways

Increasing bone resorption followed by decreasing bone mineralization are hallmarks of bone degen-eration, which mostly occurs in the elderly population and post-menopausal women. The use of mesenchymal stem cells (MSCs) has raised many promises in the field of bone regeneration due to their high osteoblastic differentiation capacity and easy availability from abundant sources. A variety of compounds, including growth factors, cytokines, and other internal factors, have been combined with MSCs to increase their osteoblastic differentiation capacity. One of these factors is melatonin, whose possible regulatory role in bone metabolism and formation has recently been suggested by many studies. Melatonin also is a potential signaling molecule and can affect many of the signaling pathways involved in MSCs osteoblastic differentiation, such as activation of PI3K/AKT, BMP/Smad, MAPK, NFkB, Nrf2/HO-1, Wnt, SIRT/SOD, PERK/ATF4. Furthermore, melatonin in combination with other components such as strontium, vitamin D3, and vitamin K2 has a synergistic effect on bone microstructure and improves bone mineral density (BMD). In this review article, we aim to summarize the regulatory mechanisms of melatonin in osteoblastic differentiation of MSCs and underling involved signaling pathways as well as the clinical potential of using melatonin in bone degenerative disorders.(c) 2022 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

Automated summary

Increasing bone resorption and decreasing bone mineralization are common features of bone degeneration, especially in the elderly and post-menopausal women. Mesenchymal stem cells (MSCs) have shown great potential in bone regeneration due to their ability to differentiate into osteoblasts and easy availability. Recent studies have suggested that melatonin, a signaling molecule, may play a regulatory role in bone metabolism and formation. It can affect multiple signaling pathways involved in MSCs' osteoblastic differentiation, and when combined with other components such as strontium, vitamin D3, and vitamin K2, it has a synergistic effect on bone microstructure and density.