Protective Role of Melatonin Against Postmenopausal Bone Loss via Enhancement of Citrate Secretion From Osteoblasts

Da, Wacili; Lin, Tao; Wen, Kaicheng; Tao, Zhengbo; Wang, Shaojie; Zhu, Yue

doi:10.3389/fphar.2020.00667

Cited by 19 publications

(16 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although some studies of the effectiveness of MT on menopausal OP have been published, researchers generally have administered MT at the time of ovariectomy (OVX) [ 17 , 19 , 23 , 24 ], or after OP had already become established [ 20 , 25 ]. Systematic analysis of changes in bone mass and bone metabolism with time after OVX was lacking and the effects of MT in different stages of the menopause are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis

et al. 2022

View full text Add to dashboard Cite

Background Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown. Methods Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes (Runx2, Sp7) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (Col1a1, Runx2, Alpl, and Bglap) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis. Results Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 μmol/L melatonin increased the mRNA expression of Col1a1, Runx2, and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis. Conclusions Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs.

show abstract

Section: Introductionmentioning

confidence: 99%

Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…This evidence indicated the potential role of melatonin in the evaluation of bone mass and strength. Additionally, our previous studies also revealed the positive effect of melatonin on osteoblasts and its therapeutic effect in postmenopausal osteoporosis in animals (Da et al, 2020;Wen et al, 2020). Oral administration of melatonin could increase the serum level of melatonin to improve bone mass (Guan et al, 2022).…”

Section: Introductionmentioning

confidence: 89%

The role of melatonin in the development of postmenopausal osteoporosis

Yang

Qiu²,

Cao³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Melatonin is an important endogenous hormone that modulates homeostasis in the microenvironment. Recent studies have indicated that serum melatonin levels are closely associated with the occurrence and development of osteoporosis in postmenopausal women. Exogenous melatonin could also improve bone mass and increase skeletal strength. To determine the underlying mechanisms of melatonin in the prevention and treatment of postmenopausal osteoporosis, we performed this review to analyze the role of melatonin in bone metabolism according to its physiological functions. Serum melatonin is related to bone mass, the measurement of which is a potential method for the diagnosis of osteoporosis. Melatonin has a direct effect on bone remodeling by promoting osteogenesis and suppressing osteoclastogenesis. Melatonin also regulates the biological rhythm of bone tissue, which benefits its osteogenic effect. Additionally, melatonin participates in the modulation of the bone microenvironment. Melatonin attenuates the damage induced by oxidative stress and inflammation on osteoblasts and prevents osteolysis from reactive oxygen species and inflammatory factors. As an alternative drug for osteoporosis, melatonin can improve the gut ecology, remodel microbiota composition, regulate substance absorption and maintain metabolic balance, all of which are beneficial to the health of bone structure. In conclusion, our review systematically demonstrates the effects of melatonin on bone metabolism. Based on the evidence in this review, melatonin will play a more important role in the diagnosis, prevention and treatment of postmenopausal osteoporosis.

show abstract

“…The combined product is chemically stable, and free radicals combined with melatonin cannot be regenerated. Our previous study revealed that intragastric melatonin could significantly improve bone mass in postmenopausal mice ( Da et al, 2020 ). Melatonin could enhance osteogenic effects by increasing SIRT1 and SIRT3, the essential factors regulating antioxidant enzyme formation in mitochondria ( Qiu et al, 2019 ; Zhou et al, 2019 ; Chen et al, 2020b ).…”

Section: Antioxidant Substancesmentioning

confidence: 99%

Three Classes of Antioxidant Defense Systems and the Development of Postmenopausal Osteoporosis

et al. 2022

Self Cite

View full text Add to dashboard Cite

Osteoporosis is a common bone imbalance disease that threatens the health of postmenopausal women. Estrogen deficiency accelerates the aging of women. Oxidative stress damage is regarded as the main pathogenesis of postmenopausal osteoporosis. The accumulation of reactive oxygen species in the bone microenvironment plays a role in osteoblast and osteoclast apoptosis. Improving the oxidative state is essential for the prevention and treatment of postmenopausal osteoporosis. There are three classes of antioxidant defense systems in the body to eliminate free radicals and peroxides including antioxidant substances, antioxidant enzymes, and repair enzymes. In our review, we demonstrated the mechanism of antioxidants and their effect on bone metabolism in detail. We concluded that glutathione/oxidized glutathione (GSH/GSSG) conversion involved the PI3K/Akt-Nrf2/HO-1 signaling pathway and that the antioxidant enzyme-mediated mitochondrial apoptosis pathway of osteoblasts was necessary for the development of postmenopausal osteoporosis. Since the current therapeutic effects of targeting bone cells are not significant, improving the systemic peroxidation state and then regulating bone homeostasis will be a new method for the treatment of postmenopausal osteoporosis.

show abstract

Protective Role of Melatonin Against Postmenopausal Bone Loss via Enhancement of Citrate Secretion From Osteoblasts

Cited by 19 publications

References 30 publications

Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis

Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis

The role of melatonin in the development of postmenopausal osteoporosis

Three Classes of Antioxidant Defense Systems and the Development of Postmenopausal Osteoporosis

Contact Info

Product

Resources

About