ONCOSTATIN M EXPRESSION AND ACTIVITY IN GINGIVAL CELLS

牙周炎是一种慢性感染性疾病，在人类人群中高度流行。虽然牙周炎在成人中最为常见，但几种形式的早发性牙周炎也见于儿童和青少年。了解胚胎和儿童发育过程中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。我们以前已经发现了一种多效性细胞因子，称为OSM(OSM)，它在细胞的早期发育和成熟过程中对细胞的生长、调节和分化具有重要作用。我们和其他人已经证明，OSM作为一种抗炎分子，对结缔组织和骨骼具有再生活性。我们最近已经证明，OSM在体内和体外的牙龈组织中都有表达，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。尽管OSM在口腔组织中的功能仍有待研究，但我们的数据表明OSM在正常牙周组织的发育和维持中可能起着重要作用。我们的研究表明，在牙周组织中诱导OSM或在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，这项拟议的研究可能为OSM的体内治疗试验、临床前试验和临床试验提供基础。此外，这项研究将进一步加深我们对儿童对口腔疾病易感性的理解，并有可能开发新的治疗干预措施。在这一应用中，我们提出了以下具体目标：1)检测OSM在儿童和成人牙周病患者血清、龈沟液和牙周活检组织中的表达水平。2)体外培养牙龈上皮细胞，观察致病细菌及诱导的促炎介质对OSM及其受体亚单位表达的影响。3)通过分析与牙周病相关的多种细胞因子、趋化因子、组织特异性基因、蛋白水解酶及其抑制物基因的表达，确定OSM对牙周成纤维细胞和牙周上皮细胞的影响。

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.