ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2017
Melatonin at pharmacological concentrations suppresses osteoclastogenesis via the attenuation of intracellular ROS.
Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- Ergothioneine prevents ovariectomy-induced osteoporosis by suppressing NF-κB/p65 signalling to attenuate osteoclastogenesis and bone marrow inflammation.Bone & joint research · 2026Article
- Melatonin: A Potential Therapy for Osteoporosis With Insights Into Molecular Mechanisms.Journal of pineal research · 2025Review
- Efficacy of Different Concentrations of Melatonin on Cultured Human Periodontal Ligament Stem Cells.Medical science monitor basic research · 2025Article
- Significant Interaction between Melatonin and Titanium Bone Implants: Available Evidence and Future Research Directions.Current pharmaceutical biotechnology · 2025Review
- Effects of Melatonin Disorders on Parkinson's Disease: A Review of Mechanisms and Clinical Manifestations.Neuropsychiatric disease and treatment · 2025Review
- Aberrant Tryptophan Metabolism Manipulates Osteochondral Homeostasis.Research (Washington, D.C.) · 2025Review
- Local application of melatonin associated or not to xenogeneic material, in critical defects of rat calvaria.Acta odontologica latinoamericana : AOL · 2024Article
- A sponge-like nanofiber melatonin-loaded scaffold accelerates vascularized bone regeneration via improving mitochondrial energy metabolism.Materials today. Bio · 2024Article
- Melatonin and oral diseases: possible therapeutic roles based on cellular mechanisms.Pharmacological reports : PR · 2024Review
- Melatonin-encapsuled silk fibroin electrospun nanofibers promote vascularized bone regeneration through regulation of osteogenesis-angiogenesis coupling.Materials today. Bio · 2024Article
- Age-related decline in melatonin contributes to enhanced osteoclastogenesis via disruption of redox homeostasis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Mechanism and application prospect of ferroptosis inhibitors in improving osteoporosis.Frontiers in endocrinology · 2024Review
- Melatonin-loaded self-healing hydrogel targets mitochondrial energy metabolism and promotes annulus fibrosus regeneration.Materials today. Bio · 2023Article
- The effects of melatonin on the viability and osteogenic/odontogenic differentiation of human stem cells from the apical papilla.Molecular biology reports · 2023Article
- The association of melatonin use and hip fracture: a matched cohort study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Article
- Melatonin suppresses bone marrow adiposity in ovariectomized rats by rescuing the imbalance between osteogenesis and adipogenesis through SIRT1 activation.Journal of orthopaedic translation · 2023Article
- Leptin and melatonin's effects on OVX rodents' bone metabolism.Frontiers in endocrinology · 2023Article
- Does Melatonin Associated with Nanostructured Calcium Phosphate Improve Alveolar Bone Repair?Medicina (Kaunas, Lithuania) · 2022Article
- Trimethylamine-N-Oxide Promotes Osteoclast Differentiation and Bone Loss via Activating ROS-Dependent NF-κB Signaling Pathway.Nutrients · 2022Article
- Psycho-Neuro-Endocrine-Immunology: A Role for Melatonin in This New Paradigm.Molecules (Basel, Switzerland) · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Osteoporosis is linked to age-related decline of melatonin production; however, the direct effects of melatonin on osteoclastogenesis remain unknown. Our study demonstrates that melatonin at pharmacological concentrations, rather than at physiological concentrations, significantly inhibits osteoclastogenesis. Melatonin-mediated anti-osteoclastogenesis involves a reactive oxygen species (ROS)-mediated but not a silent information regulator type 1 (SIRT1)-independent pathway.
introductionOsteoporosis is a bone disorder linked to impaired bone formation and excessive bone resorption. Melatonin has been suggested to treat osteoporosis due to its beneficial actions on osteoblast differentiation. However, the direct effects of melatonin on osteoclastogenesis in bone marrow monocytes (BMMs) remain unknown. This study was to investigate whether melatonin at either physiological or pharmacological concentrations could affect osteoclast differentiation.
methodsPrimary BMMs were isolated from the femurs and tibias of C57BL/6 mice and were induced toward multinucleated osteoclasts, in the presence of melatonin at either physiological (0.01 to 10 nM) or pharmacological (1 to 100 μM) concentrations. Tartrate-resistant acid phosphatase (TRAP) staining was used to label multinucleated osteoclasts and the levels of osteoclast-specific genes were evaluated. To further explore the underlying mechanisms, the roles of silent information regulator type 1 (SIRT1) and reactive oxygen species (ROS) were evaluated.
resultsWe found that melatonin at pharmacological concentrations, rather than at physiological concentrations, significantly inhibited osteoclast formation in a dose-dependent manner. The number of TRAP-positive cells and the gene expression of osteoclast-specific markers were significantly downregulated in melatonin-treated BMMs. The melatonin-mediated repression of osteoclast differentiation involved the inhibition of the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. The treatment with SIRT1 inhibitors did not affect osteoclast differentiation but, when supplemented with exogenous hydrogen peroxide, a partial rescue of melatonin-suppressed osteoclastogenesis was observed.
conclusionMelatonin at pharmacological doses directly inhibited osteoclastogenesis of BMMs by a ROS-mediated but not a SIRT1-independent pathway.
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