期刊
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
卷 69, 期 10, 页码 2564-2578出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.joms.2011.03.005
关键词
-
资金
- National Institutes of Health [5R21DE17164]
- Irving Research Scholar Grant
Purpose: Osteonecrosis of the jaws (ONJ) is a clinical condition that is characterized by a nonhealing breach in the oral mucosa resulting in exposure of bone and has been increasingly reported in patients receiving bisphosphonate (BP) therapy. Although the pathogenesis and natural history of ONJ remain ill-defined, it appears that the oral soft tissues play a critical role in the development of this condition. We examined the effects of the nitrogen-containing BPs pamidronate and zoledronate on primary human gingival fibroblasts. Materials and Methods: Primary gingival fibroblasts were exposed to clinically relevant closes of pamidronate and zoledronate. Cellular proliferation was measured with an MTS/PMS reagent- based kit (Promega, Madison, WD, scratch wound assays were performed to measure cellular migration, and apoptosis was measured by use of terminal deoxynucleotidyl transferase-mediated dUTP-FITC end labeling and caspase assays. The BP-exposed cells were treated with 10-ng/mL recombinant human platelet-derived growth factor BB (rhPDGF-BB) and 50-mu mol/L geranylgeraniol (GGOH). Results: Gingival fibroblasts are significantly more sensitive to inhibition of proliferation by zoledronate compared with pamidronate. Exposure of these cells to pamidronate but not zoledronate resulted in an increase in cellular apoptosis. Furthermore, exposure of gingival fibroblasts to pamidronate or zoledronate resulted in a decrease in cellular migration. We show that these defects are clue to a loss of cell-substratum adhesion and a reduction of F-actin bundles. Finally, we show that the addition of rhPDGF-BB and GGOH in vitro is able to partially rescue the cell proliferation, migration, and adhesion defects. Conclusion: The cytotoxic effects of BPs on oral fibroblasts and their significant reversal by the addition of GGOH and rhPDGF-BB provide both the potential mechanism and treatment options for ONJ. (C) 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:2564-2578, 2011
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据