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Zoledronic Acid Inhibits TGF-β1-Induced the Proliferation, Migration and EMT Through Smad Pathway in Human Gingival Fibroblasts

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Bisphosphonate associated osteonecrosis of the jaw (BRONJ) implies an impairment in oral hard and soft tissue repair. An understanding of the signal transduction alterations can provide therapeutic strategies for BRONJ. Transforming growth factor 1 (TGF-β1) is a critical regulator of tissue repair. Zoledronic acid (ZA) is a highly potent nitrogen-containing bisphosphonate and has a high capacity to adhere to the hydroxyapatite of mineralized dental tissues, and therefore has always been related to the development of osteonecrosis. However, the effect and mechanism of ZA on human gingival fibroblasts (HGFs) is still unknown. This study was to investigate the effect of ZA on TGF-β1-stimulated HGFs. We found that TGF-β1 significantly increased the fibroblasts proliferation and the expressions of PCNA and Ki67. All the above-mentioned cell responses were remarkably reversed by ZA. In addition, TGF-β1 induced the Smad3 signaling pathway closely related to the fibroblast migration and the differentiation of myofibroblasts. However, ZA significantly suppressed the migration of HGFs and decreased the expressions of α-smooth muscle actin and fibronectin under the stimulus of TGF-β1. In conclusion, ZA could reverse several cell responses stimulated by TGF-β1 through Smad3 signaling pathway. These results suggested that ZA could be associated with the development of bisphosphonate-induced osteonccrosis.
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Keywords: BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAWS; HUMAN GINGIVAL FIBROBLASTS; SMAD PATHWAY; TRANSFORMING GROWTH FACTOR-β1; ZOLEDRONIC ACID

Document Type: Research Article

Publication date: April 1, 2017

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  • Journal of Biomaterials and Tissue Engineering (JBT) is an international peer-reviewed journal that covers all aspects of biomaterials, tissue engineering and regenerative medicine. The journal focuses on the broad spectrum of research topics including all types of biomaterials, their properties, bioimplants and medical devices, biofilms, bioimaging, BioMEMS/NEMS, biosensors, fibers, tissue scaffolds, tissue engineering and modeling, artificial organs, tissue interfaces, interactions between biomaterials, blood, cells, tissues, and organs, regenerative medicine and clinical performance.
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