Melatonin: Another avenue for treating osteoporosis?

Tian, Li; Jiang, Shuai; Lu, Chenxi; Yang, Wenwen; Yang, Zhi; Hu, Wei; Xin, Zhenlong; Yang, Yang

doi:10.1111/jpi.12548

Cited by 104 publications

(61 citation statements)

References 143 publications

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“…As a circadian pattern, the synthesis and secretion of melatonin is regulated by the central circadian clock, which is located in the suprachiasmatic nucleus of the hypothalamus [16], and its synthesis is stimulated by the night and inhibited by light [17]. As in instances of reduced light exposure, norepinephrine is released from sympathetic nerve endings to strengthen the intracellular levels of c-AMP and activates the protein kinase A, which in term regulates the function of arylalkylamine N-acetyltransferase to limit the rates of melatonin production [15].…”

Section: Metabolism Of Melatoninmentioning

confidence: 99%

Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma

Lin

Yang

et al. 2019

Cells

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Osteosarcoma, the most common primary bone malignancy, occurs most frequently in adolescents with a peak of incidence at 11-15 years. Melatonin, an indole amine hormone, shows a wide range of anticancer activities. The decrease in melatonin levels simultaneously concurs with the increase in bone growth and the peak age distribution of osteosarcoma during puberty, so melatonin has been utilized as an adjunct to chemotherapy to improve the quality of life and clinical outcomes. While a large amount of research has been conducted to understand the complex pleiotropic functions and the molecular and cellular actions elicited by melatonin in various types of cancers, a few review reports have focused on osteosarcoma. Herein, we summarized the anti-osteosarcoma effects of melatonin and its underlying molecular mechanisms to illustrate the known significance of melatonin in osteosarcoma and to address cellular signaling pathways of melatonin in vitro and in animal models. Even in the same kind of osteosarcoma, melatonin has been sparingly investigated to counteract tumor growth, apoptosis, and metastasis through different mechanisms, depending on different cell lines. We highlighted the underlying mechanism of anti-osteosarcoma properties evoked by melatonin, including antioxidant activity, anti-proliferation, induction of apoptosis, and the inhibition of invasion and metastasis. Moreover, we discussed the drug synergy effects of the role of melatonin involved and the method to fortify the anti-cancer effects on osteosarcoma. As a potential therapeutic agent, melatonin is safe for children and adolescents and is a promising candidate for an adjuvant by reinforcing the therapeutic effects and abolishing the unwanted consequences of chemotherapies.

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Section: Metabolism Of Melatoninmentioning

confidence: 99%

Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma

Lin

Yang

et al. 2019

Cells

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“…Both melatonin and N‐acetylserotonin have protective roles in brain injury, liver damage and bone health . The Notum protein is expressed in bone, liver and brain .…”

Section: Discussionmentioning

confidence: 99%

“…Being a privileged amphiphilic molecule, melatonin can rapidly access neurons and other tissues to protect neurons, maintain bone health and alleviate osteoporosis . Multiple signalling pathways may be targeted by melatonin, including Wnt signalling .…”

Section: Introductionmentioning

confidence: 99%

Structural characterization of melatonin as an inhibitor of the Wnt deacylase Notum

Zhao

Ren

Hillier

et al. 2020

Journal of Pineal Research

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The hormone melatonin, secreted from the pineal gland, mediates multiple physiological effects including modulation of Wnt/β‐catenin signalling. The Wnt palmitoleate lipid modification is essential for its signalling activity, while the carboxylesterase Notum can remove the lipid from Wnt and inactivate it. Notum enzyme inhibition can therefore upregulate Wnt signalling. While searching for Notum inhibitors by crystallographic fragment screening, a hit compound N‐[2‐(5‐fluoro‐1H‐indol‐3‐yl)ethyl]acetamide that is structurally similar to melatonin came to our attention. We then soaked melatonin and its precursor N‐acetylserotonin into Notum crystals and obtained high‐resolution structures (≤1.5 Å) of their complexes. In each of the structures, two compound molecules bind with Notum: one at the enzyme's catalytic pocket, overlapping the space occupied by the acyl tail of the Wnt palmitoleate lipid, and the other at the edge of the pocket opposite the substrate entrance. Although the inhibitory activity of melatonin shown by in vitro enzyme assays is low (IC50 75 µmol/L), the structural information reported here provides a basis for the design of potent and brain accessible drugs for neurodegenerative diseases such as Alzheimer's disease, in which upregulation of Wnt signalling may be beneficial.

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“…It is generally believed that the key to the treatment of osteoporosis is to restore the dynamic balance of bone metabolism, and the signal pathway between cells has become a key to research [28]. With the emergence of new signaling pathways, new types of avenue s targeting them are also emerging, such as Melatonin [29].…”

Section: Discussionmentioning

confidence: 99%

Is Romosozumab better than Teriparatide for the treatment of osteoporosis? A meta-analysis through a grade analysis of evidence

Liu¹,

Ma²,

Sun³

et al. 2019

Preprint

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Background Osteoporosis is a common systemic skeletal disease. With an ageing population, the socioeconomic effect of osteoporosis will remarkably improve. Romosozumab (EVENITYTM) is a new osteoanabolic drug, which is a humanised monoclonal antibody against sclerostin, and received its first global approval for the treatment of osteoporosis in patients at high risk of fracture in Japan on January 8, 2019. Teriparatide is the first osteoanabolic drug. However, there is no comprehensive analysis and systematic review about the efficacy and safety of the two treatment. Method Randomized controlled trials (RCTs) about our analysis were searched from electronic database, including Pubmed (1996 to June 2019), Embase (1980 to June 2019), Cochrane Library (CENTRAL, June 2019), Web of Science (1998 to June 2019) and others. Four studies were included in our meta-analysis. Results Four studies containing 1304 patients meet our selection criteria. Our result of analysis indicated that Romosozumab showed better effects in improving BMD of lumbar spine (month 6: MD=3.54, 95% CI [3.13, 3.94], P<0.00001; month 12: MD=4.93, 95% CI [4.21, 5.64], P<0.00001), total hip (month 6: MD=2.27, 95% CI [0.62, 3.91], P=0.007; month 12: MD=3.17, 95% CI [2.68, 3.65], P<0.00001) and femoral neck (month 6: MD=2.30, 95% CI [0.51, 4.08], P=0.01; month 12: MD=3.04, 95% CI [2.29, 3.78], P<0.00001). And the injection-site reaction was fewer (month 12: RR=2.84, 95% CI [1.22, 6.59], P=0.02).But there were no significant differences in the incidence of serious adverse events (month 12: RR=0.78, 95% CI [0.46, 1.33], P=0.37), and death (month 12: RR=0.61, 95% CI [0.08, 4.62], P=0.63). Conclusion Based on the available studies, our current results demonstrated that Romosozumab was better than Teriparatide both in terms of efficacy and side effects.

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Melatonin: Another avenue for treating osteoporosis?

Cited by 104 publications

References 143 publications

Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma

Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma

Structural characterization of melatonin as an inhibitor of the Wnt deacylase Notum

Is Romosozumab better than Teriparatide for the treatment of osteoporosis? A meta-analysis through a grade analysis of evidence

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