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Bisphosphonate effects on the behaviour of oral epithelial cells and oral fibroblasts

2010; Elsevier BV; Volume: 56; Issue: 5 Linguagem: Inglês

10.1016/j.archoralbio.2010.11.003

1879-1506

Matthew J. Ravosa, Jie Ning, Yueying Liu, M. Sharon Stack,

Oral and Maxillofacial Pathology

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.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.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.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.