Trabandt A, Gay R E, Sukhatme V P, Gay S
Research Center of Oral Biology, School of Dentistry, University of Albama, Birmingham.
J Oral Pathol Med. 1992 May;21(5):232-40. doi: 10.1111/j.1600-0714.1992.tb00108.x.
In view of the important role of fibroblast-type collagenase in the pathogenesis of periodontal disease (PD), we investigated the expression of this metalloproteinase in primary cultures of non-stimulated fibroblasts dissected from gingival tissues of patients with generalized moderate and localized severe chronic adult PD. Enhanced hybridization signals for collagenase RNA were observed in 8/8 PD-cases when compared with equivalent RNA amounts extracted from normal fibroblasts. Since both the proto-oncogene c-fos and the "early growth response" gene egr-1 might be involved in the transcriptional regulation of the collagenase gene expression in vivo, we also compared the relative expression of both potential transcriptional factors with collagenase RNA in the same fibroblast cytoplasmic extracts. Hybridization signals indicated elevated RNA amounts for c-fos in 8/8 PD-cases and for egr-1 in 7/8 PD-cases when compared with the cells from non-inflamed tissue. In periodontitis gingival tissue specimens, immunolocalization of collagenase could be confirmed in fibroblasts, macrophages and epithelial cells in situ. Collagenase label was not widely distributed within the tissues, but concentrated at the interface between epithelium and connective tissue. The data provide the first evidence that gingival fibroblasts producing elevated levels of collagenase RNA amounts express also c-fos and egr-1 indicating a crucial role for both genes in cellular proliferation and collagenase expression in gingival and periodontal tissue destruction in vivo.
鉴于成纤维细胞型胶原酶在牙周病(PD)发病机制中的重要作用,我们研究了从患有广泛性中度和局限性重度慢性成人牙周病患者牙龈组织中分离出的未刺激成纤维细胞原代培养物中这种金属蛋白酶的表达情况。与从正常成纤维细胞中提取的等量RNA相比,在8/8例牙周病病例中观察到胶原酶RNA的杂交信号增强。由于原癌基因c-fos和“早期生长反应”基因egr-1可能都参与体内胶原酶基因表达的转录调控,我们还在相同的成纤维细胞胞质提取物中比较了这两种潜在转录因子与胶原酶RNA的相对表达情况。杂交信号表明,与来自未发炎组织的细胞相比,8/8例牙周病病例中c-fos的RNA量升高,7/8例牙周病病例中egr-1的RNA量升高。在牙周炎牙龈组织标本中,可在原位的成纤维细胞、巨噬细胞和上皮细胞中证实胶原酶的免疫定位。胶原酶标记物在组织内分布不广泛,而是集中在上皮和结缔组织的界面处。这些数据首次证明,产生高水平胶原酶RNA量的牙龈成纤维细胞也表达c-fos和egr-1,表明这两个基因在体内牙龈和牙周组织破坏中的细胞增殖和胶原酶表达中起关键作用。