title: Skeletal Site-specific Effects of Zoledronate on in vivo Bone Remodeling and in vitro BMSCs Osteogenic Activity.
abstract: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone quantity in bone remodeling following injury in the same individuals, shown as increased cortical bone thickness, increased trabecular bone formation and accelerated bone defect repair. We find that the RANKL/OPG ratio and Wnt-3a expression are suppressed at the extracted alveolar sites in Zol-treated rats compared with those at the injured sites of peripheral bones. We also show that Zol-treated bone marrow stromal cell (BMSCs) derived from jaw and peripheral bones exhibit differences in cell proliferation, alkaline phosphatase (ALP) activity, expression of osteogenic and chondrogenic related marker genes, and in vivo bone formation capacity. Hopefully, this study will help us better understand the pathogenesis of BRONJ, and deepen the theoretical research.
authors.affiliation: Department of Prosthodontics, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Prosthodontics, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China.
authors.forename: Wanlu
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Prosthodontics, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Prosthodontics, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Prosthodontics, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sheng
mesh_terms: D016301:Alveolar Bone Loss / Q000188:drug therapy*; D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000188:drug therapy*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008437:Maxilla / Q000473:pathology* / Q000601:surgery; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000473:pathology*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D053244:Osteoprotegerin; D053245:RANK Ligand; D060509:Wnt3A Protein; D000077211:Zoledronic Acid