Francisco Javier Manzano-Moreno1, Javier Ramos-Torrecillas2, Elvira De Luna-Bertos2, Candela Reyes-Botella3, Olga García-Martínez4, Concepción Ruiz5. 1. Assistant Professor, Department of Stomatology, University of Granada, Granada, Spain. 2. Assistant Professor, Department of Nursing, Faculty of Health Sciences, University of Granada, Granada, Spain. 3. Associate Professor, Professor, Department of Stomatology, University of Granada, Granada, Spain. 4. Associate Professor, Department of Nursing, Faculty of Health Sciences, University of Granada, Granada, Spain. 5. Professor, Department of Nursing, Faculty of Health Sciences, University of Granada, Granada, Spain. Electronic address: crr@ugr.es.
Abstract
PURPOSE: To evaluate the role of osteoblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ) by studying the effects of different concentrations of clodronate, a non-nitrogen-containing bisphosphonate, on osteoblast growth, differentiation, and antigenic profile. MATERIALS AND METHODS: Osteoblast-like cells (MG63) were incubated in culture medium with different doses of clodronate. Their proliferative capacity was determined with a spectrophotometric technique (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium assay). Flow cytometry was used to study the antigenic profile. Cell differentiation was evaluated by nodule formation and alkaline phosphatase (ALP) activity was measured by spectrophotometric assay. RESULTS: Clodronate had a significant stimulatory effect on osteoblast-like cell (MG63) proliferation (P < .05). A significant decrease in the expression of CD54, CD80, CD86, and HLA-DR membrane antigens versus controls was observed after 24 hours of treatment with the different clodronate doses assayed (P < .05). A significant decrease (P = .004) in ALP activity was found after 24 hours of treatment with the lowest dose (10(-9) mol/L), and a significant decrease in calcium deposition was found after 15 and 21 days of treatment (P < .05). CONCLUSION: Clodronate increases the proliferation of MG63 osteoblast-like cells and decreases their differentiation capacity, generally at low doses, and modulates the expression of costimulatory molecules associated with immune function. Clodronate exerts its effect on osteoblasts by altering their physiology and impairing their repair capacity, which could be related to the development of BRONJ. However, further research is warranted to elucidate fully the mechanisms by which bisphosphonates can produce this disease.
PURPOSE: To evaluate the role of osteoblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ) by studying the effects of different concentrations of clodronate, a non-nitrogen-containing bisphosphonate, on osteoblast growth, differentiation, and antigenic profile. MATERIALS AND METHODS: Osteoblast-like cells (MG63) were incubated in culture medium with different doses of clodronate. Their proliferative capacity was determined with a spectrophotometric technique (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium assay). Flow cytometry was used to study the antigenic profile. Cell differentiation was evaluated by nodule formation and alkaline phosphatase (ALP) activity was measured by spectrophotometric assay. RESULTS:Clodronate had a significant stimulatory effect on osteoblast-like cell (MG63) proliferation (P < .05). A significant decrease in the expression of CD54, CD80, CD86, and HLA-DR membrane antigens versus controls was observed after 24 hours of treatment with the different clodronate doses assayed (P < .05). A significant decrease (P = .004) in ALP activity was found after 24 hours of treatment with the lowest dose (10(-9) mol/L), and a significant decrease in calcium deposition was found after 15 and 21 days of treatment (P < .05). CONCLUSION:Clodronate increases the proliferation of MG63 osteoblast-like cells and decreases their differentiation capacity, generally at low doses, and modulates the expression of costimulatory molecules associated with immune function. Clodronate exerts its effect on osteoblasts by altering their physiology and impairing their repair capacity, which could be related to the development of BRONJ. However, further research is warranted to elucidate fully the mechanisms by which bisphosphonates can produce this disease.
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: Henrik Holtmann; Julian Lommen; Norbert R Kübler; Christoph Sproll; Majeed Rana; Patrick Karschuck; Rita Depprich Journal: J Int Med Res Date: 2018-08-09 Impact factor: 1.671
Authors: Francisco Javier Manzano-Moreno; Rebeca Illescas-Montes; Lucia Melguizo-Rodriguez; Victor J Costela-Ruiz; Olga García-Martínez; Concepción Ruiz; Javier Ramos-Torrecillas Journal: Int J Med Sci Date: 2019-10-21 Impact factor: 3.738
Authors: Manuel Toledano-Osorio; Francisco J Manzano-Moreno; Manuel Toledano; Antonio L Medina-Castillo; Victor J Costela-Ruiz; Concepción Ruiz; Raquel Osorio Journal: Polymers (Basel) Date: 2021-03-28 Impact factor: 4.329