title: Cytoprotective effects of melatonin on zoledronic acid-treated human mesenchymal stem cells in vitro.
abstract: OBJECTIVE
  Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a common clinical complication in patients receiving bisphosphonate therapy. Furthermore, melatonin has been proposed as a therapeutic drug for the oral cavity due to its antioxidant properties. This study aimed to evaluate the cytoprotective effects of melatonin on zoledronic acid (ZA)-treated human mesenchymal stem cells from periodontal ligament (PDLSCs) and bone marrow (BMMSCs).
  
  
  METHODS
  PDLSCs and BMMSCs were exposed to ZA, melatonin or ZA + melatonin for 72 h. Cell proliferation was measured by a colorimetric assay, whereas their mesenchymal phenotype was analyzed by flow cytometry.
  
  
  RESULTS
  Proliferation assays showed that BMMSCs presented higher ZA resistance than PDLSCs, as well as a difference in response to the simultaneous treatment of ZA + melatonin. Using PDLSCs, high doses of melatonin significantly increased their proliferation, whereas lower concentrations were enough to enhance ZA-treated BMMSC proliferation. Moreover, PDLSCs displayed a CD90/CD105 downregulation and CD73 upregulation in response to ZA, which was more pronounced in response to melatonin. Furthermore, ZA or ZA + low doses of melatonin induced a decrease of expression of CD90/CD105/CD73 on BMMSCs, while a higher concentration recovered CD73 levels.
  
  
  CONCLUSIONS
  These results suggest that melatonin has a cytoprotective effect on ZA-treated PDLSCs and BMMSCs. Thus, it could be used for BRONJ prevention.
authors.affiliation: Hematopoietic Transplant and Cellular Therapy Unit, Hematology Department, Virgen de la Arrixaca Clinical University Hospital, IMIB, University of Murcia, Spain; School of Dentistry, Faculty of Medicine, University of Murcia, Spain. Electronic address: fcojavier@um.es.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Rodríguez-Lozano
authors.affiliation: Hematopoietic Transplant and Cellular Therapy Unit, Hematology Department, Virgen de la Arrixaca Clinical University Hospital, IMIB, University of Murcia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: García-Bernal
authors.affiliation: Hematopoietic Transplant and Cellular Therapy Unit, Hematology Department, Virgen de la Arrixaca Clinical University Hospital, IMIB, University of Murcia, Spain.
authors.forename: Maria de Los Ángeles
authors.initials: Mde L
authors.lastname: Ros-Roca
authors.affiliation: Hematopoietic Transplant and Cellular Therapy Unit, Hematology Department, Virgen de la Arrixaca Clinical University Hospital, IMIB, University of Murcia, Spain.
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Algueró
authors.affiliation: School of Dentistry, Faculty of Medicine, University of Murcia, Spain.
authors.forename: Ricardo Elías
authors.initials: RE
authors.lastname: Oñate-Sánchez
authors.affiliation: School of Dentistry, Faculty of Medicine, University of Murcia, Spain.
authors.forename: Fabio
authors.initials: F
authors.lastname: Camacho-Alonso
authors.affiliation: Hematopoietic Transplant and Cellular Therapy Unit, Hematology Department, Virgen de la Arrixaca Clinical University Hospital, IMIB, University of Murcia, Spain.
authors.forename: Jose María
authors.initials: JM
authors.lastname: Moraleda
mesh_terms: D015720:5'-Nucleotidase / Q000187:drug effects; D000975:Antioxidants / Q000494:pharmacology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003124:Colorimetry / Q000379:methods; D019610:Cytoprotection; D004164:Diphosphonates / Q000494:pharmacology*; D000071063:Endoglin / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods; D058851:GPI-Linked Proteins / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D008858:Microscopy, Phase-Contrast; D010513:Periodontal Ligament / Q000166:cytology; D010641:Phenotype; D018800:Thy-1 Antigens / Q000187:drug effects; D013997:Time Factors; D000077211:Zoledronic Acid
chemical_list: D000975:Antioxidants; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; C064206:ENG protein, human; D000071063:Endoglin; D058851:GPI-Linked Proteins; D007093:Imidazoles; D018800:Thy-1 Antigens; D000077211:Zoledronic Acid; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D008550:Melatonin
keywords: Bone marrow stem cells; Melatonin; Periodontal ligament stem cells; Zoledronic acid