ArticleStem cell research & therapy2022
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.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 77 citations in OpenAlex.
- Clinical, radiographic and histomorphometric assessment of the effects of melatonin gel mixed with a xenograft in augmentation of the maxillary sinus: a randomized controlled clinical trial.BMC oral health · 2026Trial
- Histological evaluation of pulpal healing following direct pulp capping with polytetrafluoroethylene or melatonin, with or without adjunctive low-level laser therapy in Wistar rat molars.Scientific reports · 2026Article
- FGFR1 frameshift mutation mediates the dysfunction of mesenchymal stem cells in craniofacial microsomia.Stem cell research & therapy · 2026Article
- Melatonin and the Dental Pulp: A Scoping Review.International endodontic journal · 2026Article
- Effect of melatonin on the osteogenic differentiation of periodontal ligament stem cells: in vitro study.BMC oral health · 2025Article
- Senescence of dental pulp stem cells: phenotypes, underlying mechanisms and regulatory molecules.Human cell · 2025Review
- Melatonin: A Potential Therapy for Osteoporosis With Insights Into Molecular Mechanisms.Journal of pineal research · 2025Review
- The dual role of titanium particles in osteolysis: implications for gene therapy in prosthesis loosening.European journal of medical research · 2025Article
- Melatonin Increased Autophagy Level to Facilitate Osteogenesis of Inflamed PDLSCs Through TMEM110 Signaling Pathways.Journal of pineal research · 2025Article
- Programmed Transformation of Osteogenesis Microenvironment by a Multifunctional Hydrogel to Enhance Repair of Infectious Bone Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Significant Interaction between Melatonin and Titanium Bone Implants: Available Evidence and Future Research Directions.Current pharmaceutical biotechnology · 2025Review
- Melatonin: The potential avenues in dentistry.F1000Research · 2025Review
- Tissue origin dictates functional diversity of BMSC-derived EVs in bone regeneration.Frontiers in cell and developmental biology · 2025Article
- Yes-associated protein-mediated melatonin regulates the function of periodontal ligament stem cells under oxidative stress conditions.World journal of stem cells · 2024Article
- Therapeutic potential of melatonin-pretreated human dental pulp stem cells (hDPSCs) in an animal model of spinal cord injury.Scientific reports · 2024Article
- Dental pulp stem cells-derived cannabidiol-treated organoid-like microspheroids show robust osteogenic potential via upregulation of WNT6.Communications biology · 2024Article
- Differentiation of mesenchymal stem cells into vascular endothelial cells in 3D culture: a mini review.Molecular biology reports · 2024Review
- Effects ofInternational journal of molecular sciences · 2024Article
- A sponge-like nanofiber melatonin-loaded scaffold accelerates vascularized bone regeneration via improving mitochondrial energy metabolism.Materials today. Bio · 2024Article
- Amino acid-based supramolecular chiral hydrogels promote osteogenesis of human dental pulp stem cells via the MAPK pathway.Materials today. Bio · 2024Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMesenchymal stem cell (MSC)-based tissue engineering plays a major role in regenerative medicine. However, the efficiency of MSC transplantation and survival of engrafted stem cells remain challenging. Melatonin can regulate MSC biology. However, its function in the osteogenic differentiation of dental pulp-derived MSCs (DPSCs) remains unclear. We investigated the effects and mechanisms of melatonin on the osteogenic differentiation and bone regeneration capacities of DPSCs.
methodsThe biological effects and signaling mechanisms of melatonin with different concentrations on DPSCs were evaluated using a proliferation assay, the quantitative alkaline phosphatase (ALP) activity, Alizarin red staining, a real-time polymerase chain reaction, and a western blot in vitro cell culture model. The in vivo bone regeneration capacities were assessed among empty control, MBCP, MBCP + DPSCs, and MBCP + DPSCs + melatonin preconditioning in four-created calvarial bone defects by using micro-computed tomographic, histological, histomorphometric, and immunohistochemical analyses after 4 and 8 weeks of healing.
resultsIn vitro experiments revealed that melatonin (1, 10, and 100 μM) significantly and concentration-dependently promoted proliferation, surface marker expression (CD 146), ALP activity and extracellular calcium deposition, and osteogenic gene expression of DPSCs (p < 0.05). Melatonin activated the protein expression of ALP, OCN, and RUNX-2 and inhibited COX-2/NF-κB expression. Furthermore, the phosphorylation of mitogen-activated protein kinase (MAPK) p38/ERK signaling was significantly increased in DPSCs treated with 100 μM melatonin, and their inhibitors significantly decreased osteogenic differentiation. In vivo experiments demonstrated that bone defects implanted with MBCP bone-grafting materials and melatonin-preconditioned DPSCs exhibited significantly greater bone volume fraction, trabecular bone structural modeling, new bone formation, and osteogenesis-related protein expression than the other three groups at 4 and 8 weeks postoperatively (p < 0.05).
conclusionsThese results suggest that melatonin promotes the proliferation and osteogenic differentiation of DPSCs by regulating COX-2/NF-κB and p38/ERK MAPK signaling pathways. Preconditioning DPSCs with melatonin before transplantation can efficiently enhance MSCs function and regenerative capacities.
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