Häkkinen L, Strassburger S, Kähäri V M, Scott P G, Eichstetter I, Lozzo R V, Larjava H
Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, Canada.
Lab Invest. 2000 Dec;80(12):1869-80. doi: 10.1038/labinvest.3780197.
Decorin is a small leucine-rich proteoglycan that interacts with several matrix molecules, including various types of collagen and growth factors, and suppresses the growth of neoplastic cells by an epidermal growth factor (EGF) receptor-mediated pathway. Decorin is abundantly expressed in the periodontal connective tissues during development and tissue maintenance. In periodontal disease, which is one of the most common diseases in the human kind, the level of decorin is decreased in the periodontal connective tissue. Abnormal expression of decorin may also associate with certain inherited disorders that involve increased susceptibility to severe periodontal disease in the early childhood. Therefore, we investigated the periodontal tissues of mice with targeted disruption of the decorin gene. Gross and microscopic analyses showed that decorin-deficient mice appeared to have normal tooth development and eruption, and there were no signs of periodontal disease. However, electron microscopic analysis revealed abnormal morphology and organization of the collagen fibrils in the periodontal ligament. The number of periodontal ligament fibroblasts in the decorin-deficient mice was also increased about two-fold as compared with the wild-type mice. In cell culture, ectopic overexpression of decorin in NIH 3T3 fibroblasts or decorin added exogenously to periodontal fibroblasts suppressed cell growth. However, blocking the EGF receptor tyrosine kinase activity did not prevent the decorin-elicited growth suppression in periodontal fibroblasts. Additionally, decorin did not induce a marked increase in the relative expression of p21 mRNA in periodontal fibroblasts. Therefore, decorin appeared to regulate growth of normal periodontal fibroblasts by a mechanism distinct from that reported for neoplastic cells. The findings demonstrate that decorin plays a role in the organization of collagen fibrils and regulates cell proliferation in the periodontal ligament.
核心蛋白聚糖是一种富含亮氨酸的小分子蛋白聚糖，它与多种基质分子相互作用，包括各种类型的胶原蛋白和生长因子，并通过表皮生长因子（EGF）受体介导的途径抑制肿瘤细胞的生长。在发育和组织维持过程中，核心蛋白聚糖在牙周结缔组织中大量表达。牙周病是人类最常见的疾病之一，在牙周结缔组织中，核心蛋白聚糖的水平会降低。核心蛋白聚糖的异常表达也可能与某些遗传性疾病有关，这些疾病会增加儿童早期患严重牙周病的易感性。因此，我们研究了核心蛋白聚糖基因靶向破坏的小鼠的牙周组织。大体和显微镜分析表明，缺乏核心蛋白聚糖的小鼠牙齿发育和萌出似乎正常，没有牙周病的迹象。然而，电子显微镜分析显示牙周韧带中胶原纤维的形态和组织结构异常。与野生型小鼠相比，缺乏核心蛋白聚糖的小鼠牙周韧带成纤维细胞数量也增加了约两倍。在细胞培养中，NIH 3T3成纤维细胞中核心蛋白聚糖的异位过表达或外源性添加到牙周成纤维细胞中的核心蛋白聚糖可抑制细胞生长。然而，阻断EGF受体酪氨酸激酶活性并不能阻止核心蛋白聚糖引起的牙周成纤维细胞生长抑制。此外，核心蛋白聚糖并未诱导牙周成纤维细胞中p21 mRNA的相对表达显著增加。因此，核心蛋白聚糖似乎通过一种不同于肿瘤细胞所报道的机制来调节正常牙周成纤维细胞的生长。这些发现表明，核心蛋白聚糖在胶原纤维的组织中起作用，并调节牙周韧带中的细胞增殖。
