Melatonin Effects on Bone Health and Regeneration

Melatonin, a pineal-derived indoleamine, has emerged as a multifaceted regulator of skeletal homeostasis and tissue repair. Beyond its chronobiological role, melatonin promotes osteogenesis by enhancing osteoblast differentiation, mineralisation and gene expression of key markers. It concurrently suppresses osteoclastogenesis through receptor-dependent and independent pathways, dampening excessive bone resorption. As a potent antioxidant, melatonin preserves redox homeostasis within the bone microenvironment, mitigating age-related and pathology-induced oxidative damage. Recent advances illustrate its synergy with biomaterial scaffolds and hydrogels to enable controlled release and targeted delivery, thereby improving bone defect repair. Collectively, these findings underscore melatonin’s potential as a therapeutic adjunct in osteoporosis, post-surgical bone regeneration and regenerative medicine applications.

Research from Nature Portfolio

A seminal study has elucidated the mechanism by which melatonin directly regulates the late stage of osteoblast differentiation. It was shown that melatonin stabilises the transcription factor Osterix by inhibiting its ubiquitin-proteasome-mediated degradation, leading to sustained Osterix activity on osteogenic promoters. This stabilisation promotes alkaline phosphatase activity and matrix mineralisation. Further investigation revealed involvement of protein kinase A and protein kinase C pathways in melatonin-induced Osterix phosphorylation and transcriptional activation. These insights provide a molecular basis for melatonin’s anabolic effects on bone and highlight its promise as an agent to enhance osteoblast function in degenerative bone disorders.

Melatonin Effects on Bone Health and Regeneration publication trend

The graph below shows the total number of articles in melatonin effects on bone health and regeneration across all publications each year (not limited to Nature Index journals).

Technical terms

Osteoblast: Bone-forming cell responsible for matrix synthesis and mineral deposition.

Osteoclast: Multinucleated cell that resorbs bone matrix to regulate bone remodelling.

Osteogenesis: Process of new bone formation by osteoblasts.

Osteoclastogenesis: Differentiation of precursor cells into osteoclasts under factors such as RANKL.

Mesenchymal stem cells (MSCs): Multipotent progenitors capable of differentiating into osteoblasts, chondrocytes and adipocytes.

Redox homeostasis: Balance between oxidative and antioxidative processes within cells.

Scaffold: Three-dimensional biomaterial framework that supports cell attachment and tissue regeneration.

References

1. Melatonin promotes osteoblast differentiation by regulating Osterix protein stability and expression. Scientific Reports (2017).
2. Chitosan modified with PAP as a promising delivery system for melatonin in the treatment of osteoporosis: targeting the divalent metal transporter 1. Journal of Biological Engineering (2024).
3. Age-related decline in melatonin contributes to enhanced osteoclastogenesis via disruption of redox homeostasis. Molecular Medicine (2024).
4. Melatonin enhances osteogenic differentiation of dental pulp mesenchymal stem cells by regulating MAPK pathways and promotes the efficiency of bone regeneration in calvarial bone defects. Stem Cell Research & Therapy (2022).