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.
OBJECTIVE:Bisphosphonates (BPs) like Zometa (ZA) are widely used to treat complications of bony metastases in cancerpatients. 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.
Authors: Matthew Cozin; Bradley M Pinker; Kimberley Solemani; Jeremy M Zuniga; Stephen C Dadaian; Serge Cremers; Regina Landesberg; Srikala Raghavan Journal: J Oral Maxillofac Surg Date: 2011-07-31 Impact factor: 1.895
Authors: Sıdıka Sinem Akdeniz; E Beyler; Y Korkmaz; E Yurtcu; U Ates; K Araz; F I Sahin; O Y Torun Journal: Clin Oral Investig Date: 2017-07-11 Impact factor: 3.573
Authors: Fernanda Gonçalves Basso; Taisa N Pansani; Diana G Soares; Lais M Cardoso; Josimeri Hebling; Carlos Alberto de Souza Costa Journal: Clin Oral Investig Date: 2017-07-08 Impact factor: 3.573
Authors: Fernanda Gonçalves Basso; Ana Paula Silveira Turrioni; Diana Gabiela Soares; Vanderlei Salvador Bagnato; Josimeri Hebling; Carlos Alberto de Souza Costa Journal: Support Care Cancer Date: 2014-05-07 Impact factor: 3.603