Uzel M I, Kantarci A, Hong H H, Uygur C, Sheff M C, Firatli E, Trackman P C
Department of Periodontology and Oral Biology, Boston University, Goldman School of Dental Medicine, MA 02118, USA.
J Periodontol. 2001 Jul;72(7):921-31. doi: 10.1902/jop.2001.72.7.921.
Drug-induced gingival overgrowth is a known side effect of certain chemotherapeutic agents used for the treatment of systemic disorders. The pathogenesis and mechanisms responsible for this condition are not fully understood. This study assesses for the presence and localization of connective tissue growth factor (CTGF) in drug-induced gingival overgrowth tissues. CTGF immunostaining was compared with sections stained with transforming growth factor (TGF)-beta1 and CD31 antibodies in order to investigate possible pathogenic mechanisms.
Gingival overgrowth samples were obtained from patients undergoing therapy with phenytoin (n = 9), nifedipine (n = 4), cyclosporin A (n = 5), and control tissues from systemically healthy donors (n = 9). Tissue sections were subjected to peroxidase immunohistochemistry and were stained with CTGF and TGF-beta1 polyclonal primary antibodies. Possible relationships between CTGF staining and angiogenesis were also studied using an anti-CD31 antibody as a marker for endothelial cells. Staining was analyzed by computer-assisted quantitative and semiquantitative methodology at 5 defined sites in all samples based on the location of specific landmarks including epithelium and underlying connective tissues.
Cellular and extracellular CTGF content in phenytoin gingival overgrowth tissues was significantly (P<0.05) higher compared to the other gingival overgrowth tissues and the controls. Higher CTGF staining in phenytoin gingival overgrowth tissues was accompanied by an increased abundance of fibroblasts and connective tissue fibers. No strong association of CTGF staining with TGF-beta1 or CD31 staining was found.
The data from the present study show significantly higher CTGF staining in phenytoin-induced gingival overgrowth tissues compared to controls, cyclosporin A-, or nifedipine-induced gingival overgrowth. Moreover, semiquantitative analyses of histologic samples support the concept that the phenytoin overgrowth tissues are fibrotic. These associations suggest a possible role for CTGF in promoting development of fibrotic lesions in phenytoin-induced gingival overgrowth.
药物性牙龈增生是用于治疗全身性疾病的某些化疗药物已知的副作用。这种情况的发病机制尚未完全明确。本研究评估结缔组织生长因子（CTGF）在药物性牙龈增生组织中的存在及定位情况。将CTGF免疫染色与用转化生长因子（TGF）-β1和CD31抗体染色的切片进行比较，以探究可能的致病机制。
从接受苯妥英治疗的患者（n = 9）、硝苯地平治疗的患者（n = 4）、环孢素A治疗的患者（n = 5）获取牙龈增生样本，并从全身健康的供体获取对照组织（n = 9）。组织切片进行过氧化物酶免疫组织化学检测，并用CTGF和TGF-β1多克隆一抗染色。还使用抗CD31抗体作为内皮细胞标志物，研究CTGF染色与血管生成之间的可能关系。基于包括上皮和下方结缔组织在内的特定标志物位置，在所有样本的5个定义部位通过计算机辅助定量和半定量方法分析染色情况。
与其他牙龈增生组织及对照相比，苯妥英性牙龈增生组织中的细胞和细胞外CTGF含量显著更高（P<0.05）。苯妥英性牙龈增生组织中较高的CTGF染色伴随着成纤维细胞和结缔组织纤维数量的增加。未发现CTGF染色与TGF-β1或CD31染色有强关联。
本研究数据显示，与对照、环孢素A或硝苯地平诱导的牙龈增生相比，苯妥英诱导的牙龈增生组织中CTGF染色显著更高。此外，组织学样本的半定量分析支持苯妥英增生组织纤维化的概念。这些关联表明CTGF在促进苯妥英诱导的牙龈增生中纤维化病变发展方面可能发挥作用。
