A role for decorin in the structural organization of periodontal ligament

Decorin is a small leucine-rich proteoglycan that interacts with several ma trix molecules, including various types of collagen and growth factors, and suppresses the growth of neoplastic cells by an epidermal growth factor (E GF) receptor-mediated pathway. Decorin is abundantly expressed in the perio dontal connective tissues during development and tissue maintenance. In per iodontal disease, which is one of the most common diseases in the human kin d, the level of decorin is decreased in the periodontal connective tissue. Abnormal expression of decorin may also associate with certain inherited di sorders 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 microscopi c 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 org anization of the collagen fibrils in the periodontal ligament. The number o f periodontal ligament fibroblasts in the decorin-deficient mice was also i ncreased about two-fold as compared with the wild-type mice. In cell cultur e, ectopic overexpression of decorin in NIH 3T3 fibroblasts or decorin adde d exogenously to periodontal fibroblasts suppressed cell growth. However, b locking the EGF receptor tyrosine kinase activity did not prevent the decor in-elicited growth suppression in periodontal fibroblasts. Additionally, de corin did not induce a marked increase in the relative expression of p21 mR NA in periodontal fibroblasts. Therefore, decorin appeared to regulate grow th of normal periodontal fibroblasts by a mechanism distinct from that repo rted for neoplastic cells. The findings demonstrate that decorin plays a ro le in the organization of collagen fibrils and regulates cell proliferation in the periodontal ligament.