Francisco Javier Manzano-Moreno1, Javier Ramos-Torrecillas2, Elvira De Luna-Bertos2, Concepción Ruiz3, Olga García-Martínez2. 1. Department of Stomatology, School of Dentistry, University of Granada, Spain; Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Spain; Instituto Investigación Biosanitaria, ibs.Granada, Spain. 2. Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Spain; Instituto Investigación Biosanitaria, ibs.Granada, Spain. 3. Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Spain; Instituto Investigación Biosanitaria, ibs.Granada, Spain; Institute of Neuroscience, Parque Tecnológico Ciencias de la Salud, University of Granada, Armilla, Granada, Spain. Electronic address: crr@ugr.es.
Abstract
OBJECTIVES: The study objective was to evaluate the effect on osteoblast growth of high concentrations of three nitrogen-containing bisphosphonates (pamidronate, alendronate, and ibandronate) and one non-nitrogen-containing bisphosphonate (clodronate), using the MG-63 cell line as an osteoblast model, in order to determine the role of osteoblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIALS AND METHODS: Osteoblasts were incubated in culture medium with different doses of pamidronate, alendronate, ibandronate or clodronate. The proliferative capacity of the osteoblasts was determined by spectrophotometry (MTT-based) at 24 h of culture. Flow cytometry was used to determine the percentage of cells in each cell cycle phase (G0/G1, G2/M, and S) and to discriminate apoptotic cell death from necrotic cell death in the cell cycle at 24 h of treatment. RESULTS: All the bisphosphonates assayed produced a significant and dose-dependent reduction in MG-63 proliferation at the high doses assayed (10(-4) and 5 × 10(-5) M) in comparison with controls (p <0.001). Cell cycle study revealed that all assayed bisphosphonates significantly arrested the cell cycle in phase G0/G1 at doses of 10(-4) and 5 × 10(-5) M, increasing the percentage of cells in this phase (p <0.05). Apoptosis/necrosis studies showed significant changes compared with control cells, with an increased percentage of cells in apoptosis after treatment with 10(-4) or 5 × 10(-5) M of pamidronate, alendronate, ibandronate, or clodronate (p <0.05). CONCLUSIONS: High doses of nitrogen-containing or non-nitrogen-containing bisphosphonates can reduce the proliferation of MG-63 osteoblast-like cells by arresting the cell cycle and inducing apoptosis/necrosis.
OBJECTIVES: The study objective was to evaluate the effect on osteoblast growth of high concentrations of three nitrogen-containing bisphosphonates (pamidronate, alendronate, and ibandronate) and one non-nitrogen-containing bisphosphonate (clodronate), using the MG-63 cell line as an osteoblast model, in order to determine the role of osteoblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIALS AND METHODS: Osteoblasts were incubated in culture medium with different doses of pamidronate, alendronate, ibandronate or clodronate. The proliferative capacity of the osteoblasts was determined by spectrophotometry (MTT-based) at 24 h of culture. Flow cytometry was used to determine the percentage of cells in each cell cycle phase (G0/G1, G2/M, and S) and to discriminate apoptotic cell death from necrotic cell death in the cell cycle at 24 h of treatment. RESULTS: All the bisphosphonates assayed produced a significant and dose-dependent reduction in MG-63 proliferation at the high doses assayed (10(-4) and 5 × 10(-5) M) in comparison with controls (p <0.001). Cell cycle study revealed that all assayed bisphosphonates significantly arrested the cell cycle in phase G0/G1 at doses of 10(-4) and 5 × 10(-5) M, increasing the percentage of cells in this phase (p <0.05). Apoptosis/necrosis studies showed significant changes compared with control cells, with an increased percentage of cells in apoptosis after treatment with 10(-4) or 5 × 10(-5) M of pamidronate, alendronate, ibandronate, or clodronate (p <0.05). CONCLUSIONS: High doses of nitrogen-containing or non-nitrogen-containing bisphosphonates can reduce the proliferation of MG-63 osteoblast-like cells by arresting the cell cycle and inducing apoptosis/necrosis.
Authors: Francisco Javier Manzano-Moreno; Javier Ramos-Torrecillas; Elvira de Luna-Bertos; Rebeca Illescas-Montes; Timothy R Arnett; Concepción Ruiz; Olga García-Martínez Journal: Clin Oral Investig Date: 2018-06-06 Impact factor: 3.573
Authors: Francisco Javier Manzano-Moreno; Javier Ramos-Torrecillas; Lucia Melguizo-Rodríguez; Rebeca Illescas-Montes; Concepción Ruiz; Olga García-Martínez Journal: Int J Med Sci Date: 2018-02-12 Impact factor: 3.738
Authors: Siri Paulo; Mafalda Laranjo; Ana M Abrantes; João Casalta-Lopes; Kathleen Santos; Ana C Gonçalves; Anabela Baptista Paula; Carlos Miguel Marto; Ana Bela Sarmento-Ribeiro; Eunice Carrilho; Arménio Serra; Maria F Botelho; Manuel M Ferreira Journal: Materials (Basel) Date: 2019-06-06 Impact factor: 3.623