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。虽然牙周炎是最常见的成人，几种形式的早发性牙周炎是看到在儿童和青少年。了解胚胎期和儿童期牙周组织形成的基本生物学过程，以及成年期牙周组织的维持，对于开发预防、诊断和治疗牙周炎的新方法至关重要。我们以前已经确定了一个多效性细胞因子称为制瘤素M（OSM）（OSM），这是重要的细胞生长，调节和分化过程中的早期发育和成熟。我们和其他人已经表明，OSM作为一种抗炎分子，对结缔组织和骨具有再生活性。我们最近已经证明，OSM在体内和体外牙龈组织中表达，这种表达是下调细菌成分。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。尽管OSM在口腔组织中的功能还有待进一步研究，但我们的数据表明OSM对正常牙周组织的发育和维持可能很重要。 我们的研究表明，在牙周组织中诱导OSM或添加外源性OSM可以逆转牙周炎的疾病进展。我们相信，拟议的研究可能会提供一个基础，治疗测试OSM在体内的临床前和临床试验。此外，这项研究将进一步了解儿童对口腔疾病的易感性，并有可能开发新的治疗干预措施。在本申请中，我们提出了以下具体目标：1）确定OSM在患有牙周病的儿童和成人的血清、龈沟液和牙龈活检组织中的表达水平。2)评估周围病原菌和诱导的促炎介质在体外牙龈上皮细胞培养物中调节OSM和OSM受体亚单位表达的能力。3)通过分析与牙周病有关的各种细胞因子、趋化因子、组织特异性基因和蛋白酶及其抑制剂的基因表达，确定OSM对体外牙龈成纤维细胞和上皮细胞的影响。

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.