Therapeutic Strategies for Treating Type 2 Diabetes Mellitus -Associated Periodon

描述（由申请人提供）：糖尿病患者的牙周炎患病率是非糖尿病患者的两倍。糖尿病牙周病更严重和难治，因为T2 DM和肥胖触发释放过量的炎症因子，如TNF-1和IL-6，这反过来刺激破骨细胞再吸收支持牙齿的牙槽骨。 脂联素是一种脂肪细胞源性激素，具有调节胰岛素敏感性、抑制炎症、改善糖尿病症状等多种生物学功能。它还促进成骨细胞分化和骨形成。我们最近的研究表明脂联素抑制破骨细胞的分化，增加破骨细胞的凋亡。 我们的长期目标是确定和表征一种理想的内源性介质，作为治疗广泛流行的T2 DM相关牙周炎的有效治疗药物。本申请的目的是研究脂联素在T2 DM相关牙周炎发病机制中的作用机制，并通过体内脂联素的补充来特异性地重建炎症损伤的牙周组织。待检验的中心假设是脂联素水平的降低，以及随之而来的对破骨细胞和促炎因子的抑制作用的消除，有助于T2 DM和T2 DM相关牙周炎的发病机制。此外，全身性脂联素输注促进受损牙周组织的重建。目标1：首次采用动物模型研究抗炎因子在牙周病发病机制中的作用，包括抑制直接吸收牙槽骨的破骨细胞的分化。目标二：探讨脂联素全身灌注在抑制炎症和重建受损牙周组织中的治疗作用。 结合我们的经验和波士顿大学的Salomon Amar博士和哥伦比亚大学的Gerard Karsenty博士的专家协助，这个新项目的完成肯定会提供一个先进的基于生物工程的工具，以精确和可预测地控制炎症的解决和受损牙周组织的重建。

DESCRIPTION (provided by applicant): Periodontitis is twice as prevalent in diabetics as in non-diabetics. Diabetic periodontal diseases are more severe and refractory because T2DM and obesity trigger the release of excess inflammatory factors, such as TNF-1 and IL-6, which in turn stimulate osteoclasts to resorb the alveolar bone that supports the teeth. Adiponectin, a fat cell derived hormone, is emerging as a potent molecule with multiple biological functions including regulating insulin sensitivity, suppressing inflammation, and improving diabetic symptoms. It also promotes osteoblastic differentiation and bone formation. Our recent studies have shown that adiponectin inhibits osteoclast differentiation and increases osteoclast apoptosis. Our long-term objective is to identify and characterize an ideal endogenous mediator as a potent therapeutic remedy for the treatment of the widely prevalent T2DM-associated periodontitis. The objective of this application is to investigate the mechanisms of adiponectin in the pathogenesis of T2DM-associated periodontitis and to specifically reconstruct the inflammatorily damaged periodontal tissues by the replenishment of adiponectin in vivo. The central hypothesis to be tested is that the decreased level of adiponectin, together with the consequent removal of its suppressive effects on osteoclasts and proinflammatory factors, contributes to the pathogenesis of T2DM and T2DM-associated periodontitis. Also, a systemic adiponectin infusion promotes the reconstruction of the damaged periodontal tissues. Aim 1: Using an animal model for the first time to determine the effects of anti-inflammatory factor in periodontal pathogenesis including inhibition of differentiation of osteoclasts that directly resorb alveolar bone. Aim 2: To determine the therapeutic effect of systemic adiponectin infusion in dampening inflammation and in reconstruction of damaged periodontal tissues in vivo. Combining our experience and the expert assistance from Drs. Salomon Amar at Boston University and Gerard Karsenty at Columbia University, the completion of this novel project will definitely provide an advanced bioengineering-based tool to allow precise and predictable control of inflammatory resolution and reconstruction of damaged periodontal tissues.