Author(s): Ravosa MJ, Ning J, Liu Y, Stack MS
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Abstract OBJECTIVE: Bisphosphonates (BPs) like Zometa (ZA) are widely used to treat complications of bony metastases in cancer patients. A serious adverse event occurs in 1-12\% of patients on BP therapy, osteonecrosis of the jaw (BPONJ). BPONJ develops after oral trauma and is manifested by poor wound healing and soft-tissue breakdown followed by exposure and necrosis of intra-oral bone. Currently, there is no effective clinical treatment for BPONJ. DESIGN: We evaluated the effect of ZA on the proliferation, apoptosis and migratory capacity of the cell lines CRL-7408, an oral fibroblast culture and OKF/6, an oral epithelial cell line. RESULTS: In both oral epithelium and fibroblasts, ZA exposure inhibited proliferation and elevated apoptosis; however oral fibroblasts were differentially influenced versus oral epithelial cells. In oral fibroblasts, ZA treatment significantly inhibited motility. Further, quantitative real-time PCR demonstrated that ZA treatment of oral fibroblasts inhibits expression of both the COL1A1 and COL1A2 chains of type-I collagen, consistent with a loss of collagen immunofluorescent staining. CONCLUSIONS: These data support a model wherein ZA treatment impedes oral wound healing by blocking the growth and migratory capacity of oral fibroblasts as well as downregulating the transcription of type-I collagen, functions necessary to deposit the granulation tissue needed for re-epithelization. Therefore, BP released from bone following tooth extraction may delay wound healing of the oral mucosal barrier and contribute to BPONJ pathogenesis. Copyright © 2010 Elsevier Ltd. All rights reserved.
This article was published in Arch Oral Biol
and referenced in Journal of Biomedical Engineering and Medical Devices