ONCOSTATIN M EXPRESSION AND ACTIVITY IN GINGIVAL CELLS

牙周炎是一种在人群中高度流行的慢性感染性疾病。虽然牙周炎在成人中最常见，但在儿童和青少年中也有几种形式的早发性牙周炎。了解导致牙周组织在胚胎和儿童发育期间形成的基本生物学过程，以及它们在成年期的维持，对于开发预防、诊断和治疗牙周炎的新方法至关重要。我们之前已经发现了一种多效细胞因子，称为抑癌素M (OSM) (OSM)，它在细胞早期发育和成熟过程中的生长、调节和分化中起重要作用。我们和其他人已经表明，OSM作为一种抗炎分子，在结缔组织和骨骼方面具有再生活性。我们最近已经证明OSM在体内和体外牙龈组织中表达，并且这种表达受到细菌成分的下调。此外，我们有证据表明OSM特异性受体在几种牙周细胞类型中大量表达。虽然要确定OSM在口腔组织中的功能还有相当多的工作要做，但我们的数据表明OSM可能对正常牙周组织的发育和维持很重要。我们的研究表明，在牙周组织中诱导OSM或向牙周组织中添加外源性OSM可以逆转牙周炎的疾病进展。我们相信本研究可为OSM在体内临床前和临床试验中的治疗性测试提供基础。此外，这项研究将进一步加深我们对儿童对口腔疾病的易感性的理解，具有开发新的治疗干预措施的潜力。在本应用中，我们提出以下具体目的：1)测定儿童和成人牙周病患者血清、龈沟液和牙龈活检中OSM的表达水平。2)在体外培养的牙龈上皮细胞中，评估周围致病菌和诱导的促炎介质对OSM和OSM受体亚基表达的模块化能力。3)通过分析与牙周病相关的各种细胞因子、趋化因子、组织特异性基因、蛋白酶及其抑制剂基因的表达，确定OSM对牙龈成纤维细胞和上皮细胞的体外影响。

Periodontitis is a chronic infectious disease process which is highly prevalent in human populations. Although periodontitis is most common in adults, several forms of early onset periodontitis are seen in children and adolescents. An understanding of the basic biologic process leading to the formation of periodontal tissues during embryonic and childhood development, as well as their maintenance during adulthood is crucial doe the development of new approaches for the prevention, diagnosis and treatment of periodontitis. We have previously identified a pleiotropic cytokine called oncostatin M (OSM) (OSM) which is important in cell growth, regulation and differentiation during early development and maturation. We and others have shown that OSM acts as an anti- inflammatory molecule which has regenerative activities with regard to connective tissue and bone. We have recently demonstrated that OSM is expressed in gingival tissues in vivo and in vitro and that this expression is down-regulated by bacterial components. Furthermore, we have evidence that the OSM specific receptor is abundantly expressed in several periodontal cell types. Although considerable work remains to establish the function of OSM in oral tissues, our data suggest that OSM may be important for the development and maintenance of the normal periodontium. Our studies suggest that the induction of OSM in or the addition of exogenous OSM to periodontal tissues could reverse the disease progression in periodontitis. We believe that the proposed research may provide a basis for therapeutic testing of OSM in vivo preclinical and clinical trials. In addition, this research will further our understanding of childhood susceptibility to oral diseases, with the potential for the development of new therapeutic interventions. In this application, we propose the following specific aims: 1) Determine the expression levels of OSM in serum, gingival crevicular fluids and gingival biopsies from children and adults with periodontal disease. 2) Assess the ability of periopathogenic bacteria and induced pro-inflammatory mediators to module the expression of OSM and the OSM receptor subunits in gingival epithelial cell cultures in vitro. 3) Determine the effects of OSM on gingival fibroblast and epithelial cells in vitro by analyzing the expression of genes for various cytokines, chemokines, tissue-specific genes, and proteinases and their inhibitors which are implicated in periodontal disease.