Francisco Javier Rodríguez-Lozano1, David García-Bernal2, Maria de Los Ángeles Ros-Roca2, Maria del Carmen Algueró2, Ricardo Elías Oñate-Sánchez3, Fabio Camacho-Alonso3, Jose María Moraleda2. 1. 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. 2. Hematopoietic Transplant and Cellular Therapy Unit, Hematology Department, Virgen de la Arrixaca Clinical University Hospital, IMIB, University of Murcia, Spain. 3. School of Dentistry, Faculty of Medicine, University of Murcia, Spain.
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. CONCLUSION: These results suggest that melatonin has a cytoprotective effect on ZA-treated PDLSCs and BMMSCs. Thus, it could be used for BRONJ prevention.
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. CONCLUSION: These results suggest that melatonin has a cytoprotective effect on ZA-treated PDLSCs and BMMSCs. Thus, it could be used for BRONJ prevention.
Authors: Anna Di Vito; E Chiarella; F Baudi; P Scardamaglia; A Antonelli; D Giudice; T Barni; L Fortunato; A Giudice Journal: Cell Transplant Date: 2020 Jan-Dec Impact factor: 4.064