PORPHYROMONAS GINGIVALIS ACTIVATOR COLLAGENOLYSIS

结缔组织重塑是目前知之甚少的过程 在生长和发育过程中以及慢性 炎症性疾病（关节炎和牙周炎）和肿瘤 转移 在过去的十年中，脊椎动物酶家族被称为 基质金属蛋白酶（MMPs）被发现与这些 重塑过程。 MMPs是一个9人或更多的家庭 作为酶原分泌的锌-金属蛋白酶当被激活时， 共同降解大部分或所有已知的细胞外基质（ECM） proteins. 牙周炎是ECM重塑的独特模型， 支持牙齿的硬组织和软组织的变化是由慢性 细菌感染 在疾病过程中，牙齿支撑 靠近细菌感染的胶原纤维被降解， 牙齿周围的上皮细胞迁移到牙齿周围留下的空间中。 溶解的胶原蛋白，最终导致牙齿脱落。 的 负责这种ECM降解的酶的来源是未知的。 我们以前已经表明，活的上皮细胞（角质形成细胞） 可以刺激I型胶原纤维上的生长以降解 胶原蛋白底物通过添加细菌培养液从 牙龈卟啉单胞菌，一种与牙龈炎高度相关的微生物， 成人牙周炎发病率和严重程度。 内部因素 负责这种刺激作用牙龈卟啉单胞菌培养基 鉴定为巯基蛋白酶，并表征为聚集体 所有肽均来源于140 kDa前体的内部水解 蛋白酶。 牙龈卟啉单胞菌蛋白酶证明了 激活MMPs，包括胶原酶，当应用于肝 培养的角质形成细胞刺激MMP mRNA水平的诱导 导致高度局部化的胶原-基质降解， 角质形成细胞 这些结果是第一批定义 P. 牙龈和上皮细胞的基质重塑。 给定 细菌、上皮细胞和 胶原附着器在牙周炎中所占比例，这些数据 表明上皮细胞中MMP活化和诱导 病原菌如牙龈卟啉单胞菌可促进 牙周炎的组织破坏。

Connective tissue remodeling is, currently, a poorly understood process that occurs during growth and development as well as in the chronic inflammatory diseases (the arthritides and periodontitis) and tumor metastasis. In the past decade a family of vertebrate enzymes called matrix metalloproteinases (MMPs) were found to be associated with these remodeling processes. The MMPs are a family of nine or more zinc-metalloproteinases secreted as zymogens and when activated can, collectively, degrade most or all the known extracellular matrix (ECM) proteins. Periodontitis is a unique model for ECM remodeling because degradation of the hard and soft tissues supporting the teeth results from a chronic bacterial infection. During the disease process, tooth-supporting collagen fibers close to the bacterial infection are degraded while the epithelium surrounding the tooth migrates into the space left by the dissolved collagen, ultimately resulting in loss of the tooth. The source of the enzymes responsible for this ECM degradation is not known. We have previously shown that live epithelial cells (keratinocytes) growing on type I collagen fibers can be stimulated to degrade the collagen substrate by the addition of bacterial culture fluid from Porphyromonas gingivalis, a microorganism highly associated with the incidence and severity of periodontitis in adults. The factor within the P. gingivalis culture medium responsible for this stimulating effect was identified as a thiol-proteinase and characterized as an aggregate of peptides all derived from internal hydrolysis of a 140 kDa precursor proteinase. The P. gingivalis proteinase demonstrated the ability to activate MMPs, including collagenase, and when applied to live keratinocytes in culture stimulated the induction of MMP mRNA levels resulting in highly localized collagen--substrate degradation by the keratinocytes. These results are some of the first to define the potential relationship between proteinase activity released by P. gingivalis and epithelial cells with regard to matrix remodeling. Given the close proximity that the bacteria, the epithelium, and the collagenous attachment apparatus share in periodontitis, these data suggest that activation and induction of MMPs in the epithelial cells by pathogenic bacteria such as P. gingivalis may promote the accelerated tissue destruction in periodontitis.