Regulation effects of melatonin on bone marrow mesenchymal stem cell differentiation

Wang

Stem Cells International

et al. 2019

Accumulation of reactive oxygen species (ROS), which can be induced by inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can significantly inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). This process can contribute to the imbalance of bone remodeling, which ultimately leads to osteoporosis. Therefore, reducing the ROS generation during osteogenesis of BMSCs may be an effective way to reverse the impairment of osteogenesis. Melatonin (MLT) has been reported to act as an antioxidant during cell proliferation and differentiation, but its antioxidant effect and mechanism of action during osteogenesis of MSCs in the inflammatory microenvironment, especially in the presence of TNF-α, remain unknown and need further study. In our study, we demonstrate that melatonin can counteract the generation of ROS and the inhibitory osteogenesis of BMSCs induced by TNF-α, by upregulating the expression of antioxidases and downregulating the expression of oxidases. Meanwhile, MLT can inhibit the phosphorylation of p65 protein and block the degradation of IκBα protein, thus decreasing the activity of the NF-κB pathway. This study confirmed that melatonin can inhibit the generation of ROS during osteogenic differentiation of BMSCs and reverse the inhibition of osteogenic differentiation of BMSCs in vitro, suggesting that melatonin can antagonize TNF-α-induced ROS generation and promote the great effect of osteogenic differentiation of BMSCs. Accordingly, these findings provide more evidence that melatonin can be used as a candidate drug for the treatment of osteoporosis.

Section: Introductionmentioning

confidence: 82%

Melatonin Rescued Reactive Oxygen Species-Impaired Osteogenesis of Human Bone Marrow Mesenchymal Stem Cells in the Presence of Tumor Necrosis Factor-Alpha

Wang

Stem Cells International

et al. 2019

Journal of Pineal Research

“…Melatonin is highly pleiotropic and regulates countless physiological parameters in numerous organs. 8,[28][29][30][31] Among them, several fields deserve particular emphasis, such as the control of circadian rhythms and, in photoperiodically sensitive species, of seasonality, both in conjunction with the transmission of the signal "darkness" [32][33][34] ; modulation of differentiation and growth [35][36][37] ; antioxidative protection by various mechanisms [38][39][40][41][42] ; anti-oncogenic and oncostatic actions [43][44][45] ; and, with particular relevance to this article, immune modulation. 16,[46][47][48][49] Physiological functions of macrophages go from host defense to immune downregulation, 50,51 in addition to their homeostatic activities.…”

Section: Introductionmentioning

confidence: 99%

Melatonin in macrophage biology: Current understanding and future perspectives

Xia

Chen

Zeng

et al. 2019

145

122

Melatonin is a ubiquitous hormone found in various organisms and highly affects the function of immune cells. In this review, we summarize the current understanding of the significance of melatonin in macrophage biology and the beneficial effects of melatonin in macrophage‐associated diseases. Enzymes associated with synthesis of melatonin, as well as membrane receptors for melatonin, are found in macrophages. Indeed, melatonin influences the phenotype polarization of macrophages. Mechanistically, the roles of melatonin in macrophages are related to several cellular signaling pathways, such as NF‐κB, STATs, and NLRP3/caspase‐1. Notably, miRNAs (eg, miR‐155/‐34a/‐23a), cellular metabolic pathways (eg, α‐KG, HIF‐1α, and ROS), and mitochondrial dynamics and mitophagy are also involved. Thus, melatonin modulates the development and progression of various macrophage‐associated diseases, such as cancer and rheumatoid arthritis. This review provides a better understanding about the importance of melatonin in macrophage biology and macrophage‐associated diseases.

Journal of Pineal Research

“…We previously reviewed the roles of melatonin in cancer, ischemic heart diseases, fibrosis, and sepsis . Previous reviews have suggested that melatonin plays a pivotal role in bone . Recent studies have demonstrated that melatonin can protect against osteoporosis and maintain homeostasis of bone metabolism .…”

Section: Introductionmentioning

confidence: 99%

“…30 Previous reviews have suggested that melatonin plays a pivotal role in bone. 31,32 Recent studies have demonstrated that melatonin can protect against osteoporosis 33 and maintain homeostasis of bone metabolism. 34,35 In light of the emerging roles of melatonin in bone metabolism, the present review discusses recent breakthroughs related to melatonin in osteoporosis ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Melatonin: Another avenue for treating osteoporosis?

Tian

Jiang

et al. 2019

106

Melatonin is a signal molecule that modulates the biological circadian rhythms of vertebrates. Melatonin deficiency is thought to be associated with several disorders, including insomnia, cancer, and cardiovascular and neurodegenerative diseases. Accumulating evidence has also indicated that melatonin may be involved in the homeostasis of bone metabolism. Age‐related reductions in melatonin are considered to be critical factors in bone loss and osteoporosis with aging. Thus, serum melatonin levels might serve as a biomarker for the early detection and prevention of osteoporosis. Compared to conventional antiosteoporosis medicines, which primarily inhibit bone loss, melatonin both suppresses bone loss and promotes new bone formation. Mechanistically, by activating melatonin receptor 2 (MT2), melatonin upregulates the gene expression of alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2), BMP6, osteocalcin, and osteoprotegerin to promote osteogenesis while inhibiting the receptor activator of NF‐kB ligand (RANKL) pathway to suppress osteolysis. In view of the distinct actions of melatonin on bone metabolism, we hypothesize that melatonin may be a novel remedy for the prevention and clinical treatment of osteoporosis.