The multiple functions of melatonin in regenerative medicine

Majidinia, Maryam; Reíter, Russel J.; Shakouri, Seyed Kazem; Mohebbi, Iraj; Rastegar, Mojgan; Kaviani, Mojtaba; Darband, Saber Ghazizadeh; Jahanban‐Esfahlan, Rana; Nabavi, Seyed Mohammad; Yousefi, Bahman

doi:10.1016/j.arr.2018.04.003

Cited by 81 publications

(52 citation statements)

References 290 publications

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“…Moreover, melatonin has therapeutic potential for bone regeneration. Studies have demonstrated that melatonin can elevate bone ALP levels, increase bone mass and promote mineralization, collagen type I synthesis, new bone growth, and osteointegration . Together, these findings demonstrate that melatonin can be applied to the treatment of osteoporosis‐related diseases.…”

Section: Prospects and Conclusionmentioning

confidence: 85%

“…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%

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Melatonin: Another avenue for treating osteoporosis?

Tian

Jiang

et al. 2019

Journal of Pineal Research

111

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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.

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Section: Prospects and Conclusionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Melatonin: Another avenue for treating osteoporosis?

Tian

Jiang

et al. 2019

Journal of Pineal Research

111

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“…Currently, the length of melatonin treatment in HIE for optimal neuroprotection is unknown. Preclinical studies are necessary because new evidence shows that melatonin can enhance cell and tissue regeneration and is protective during acute neurodegeneration . The injured immature brain holds high‐level neural plasticity and could be particularly susceptible to treatment modalities such as melatonin that can trigger neuron generation (reactive neurogenesis) and creation of new neural networks.…”

Section: Discussionmentioning

confidence: 99%

Melatonin pharmacokinetics and dose extrapolation after enteral infusion in neonates subjected to hypothermia

Balduini

Weiss

Carloni

et al. 2019

Journal of Pineal Research

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Introduction Neonates with hypoxic‐ischemic encephalopathy (HIE) undergoing hypothermia may benefit from adjunctive therapy with melatonin. However, melatonin safety, pharmacokinetics (PK), and dosage in this sensitive population are still unknown. Methods and results This study assessed the PK and safety of melatonin enteral administration to neonates with HIE undergoing hypothermia. Melatonin was infused at 0.5 mg/kg in five neonates with HIE undergoing hypothermia. Infusion started 1 hour after the neonates reached the target temperature of 33.5°C. Blood samples were collected before and at selective times after melatonin infusion. Abdominal complications or clinically significant changes in patients’ vital signs were not found during or after melatonin. The peak plasma concentration reached 0.25 µg/mL. The area under the curve in 24 hours was 4.35 µg/mL*h. Discussion Melatonin half‐life and clearance were prolonged, and the distribution volume decreased compared to adults. In silico simulation estimated that the steady state can be reached after four infusions. Hypothermia does not affect melatonin PK. In humans high blood concentrations with lower doses can be achieved compared to animal experimentation, although intravenous administration is advised in the neonate population. Our study is a preparatory step for future clinical studies aimed at assessing melatonin efficacy in HIE.

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“…A derivative of Tryptophan, melatonin is an important signal molecule with wide natural distribution and with a broad range of biological functions: the regulation of the immune system, neuroprotection, antioxidant, anti-inflammation, oncostatic, regulation of pituitary hormones as well as regulatory effects on circadian and endocrine rhythms (Majidinia et al, 2018[23]). The beneficial effects of melatonin on peripheral nerve injury have been indicated in several studies.…”

Section: Discussionmentioning

confidence: 99%