Caroline A Martins1, Gabriele Leyhausen1, Joachim Volk1, Werner Geurtsen2. 1. Department of Conservative/Preventive Dentistry and Periodontology, Hannover Medical School, Hannover, Germany. 2. Department of Conservative/Preventive Dentistry and Periodontology, Hannover Medical School, Hannover, Germany. Electronic address: Geurtsen.Werner@mh-hannover.de.
Abstract
INTRODUCTION: Root resorption is a common complication after replantation following traumatic dental avulsion. Endodontic therapy combined with local and intracanal medications aims to avoid osteoclastic activity. In such cases, the application of alendronate (ALN), a bisphosphonate widely used for the treatment of bone disorders, could be of clinical relevance. This study evaluated alendronate biocompatibility on periodontal ligament cells as well as its effects on an in vitro osteoclastogenesis model. METHODS: Alendronate cytotoxicity (10(-3) to 10(-9) mol/L) in human periodontal ligament fibroblasts, human osteogenic sarcoma cells, and murine osteoclastic precursors (RAW 264.7) was analyzed using cell number determination, cell viability, and proliferation assays. ALN (10(-6) to 10(-12) mol/L) effects on RANKL-induced osteoclastogenesis of RAW cells were assessed by tartrate-resistant acid phosphatase (TRAP) staining and activity and real-time polymerase chain reaction. RESULTS: ALN at higher concentrations was cytotoxic for all cell types, inhibiting significantly the proliferation of human osteogenic sarcoma cells and human periodontal ligament fibroblasts (≥10(-5) mol/L). TRAP activity and expression of the osteoclast markers TRAP and cathepsin K by RAW-derived osteoclasts decreased significantly with ALN at low concentrations, reaching the maximum effect at 10(-10) mol/L. CONCLUSIONS: We showed that ALN at very low concentrations is an effective inhibitor of RANKL-generated osteoclasts, without causing cytotoxic effects on their precursors or periapical cells. ALN at such concentrations might be useful to prevent replacement resorption in avulsed teeth.
INTRODUCTION: Root resorption is a common complication after replantation following traumatic dental avulsion. Endodontic therapy combined with local and intracanal medications aims to avoid osteoclastic activity. In such cases, the application of alendronate (ALN), a bisphosphonate widely used for the treatment of bone disorders, could be of clinical relevance. This study evaluated alendronate biocompatibility on periodontal ligament cells as well as its effects on an in vitro osteoclastogenesis model. METHODS:Alendronatecytotoxicity (10(-3) to 10(-9) mol/L) in human periodontal ligament fibroblasts, humanosteogenic sarcoma cells, and murineosteoclastic precursors (RAW 264.7) was analyzed using cell number determination, cell viability, and proliferation assays. ALN (10(-6) to 10(-12) mol/L) effects on RANKL-induced osteoclastogenesis of RAW cells were assessed by tartrate-resistant acid phosphatase (TRAP) staining and activity and real-time polymerase chain reaction. RESULTS:ALN at higher concentrations was cytotoxic for all cell types, inhibiting significantly the proliferation of humanosteogenic sarcoma cells and human periodontal ligament fibroblasts (≥10(-5) mol/L). TRAP activity and expression of the osteoclast markers TRAP and cathepsin K by RAW-derived osteoclasts decreased significantly with ALN at low concentrations, reaching the maximum effect at 10(-10) mol/L. CONCLUSIONS: We showed that ALN at very low concentrations is an effective inhibitor of RANKL-generated osteoclasts, without causing cytotoxic effects on their precursors or periapical cells. ALN at such concentrations might be useful to prevent replacement resorption in avulsed teeth.
Authors: Vivian Bradaschia-Correa; Giovanna C Ribeiro-Santos; Lorraine Perciliano de Faria; Paula Rezende-Teixeira; Victor E Arana-Chavez Journal: J Mol Histol Date: 2022-06-14 Impact factor: 3.156
Authors: Claudia Martini; Fernando Nicolas Sosa; Ricardo Malvicini; Natalia Pacienza; Gustavo Yannarelli; María Del C Vila Journal: J Physiol Biochem Date: 2021-07-24 Impact factor: 4.158