Accelerated Osteoarthritis in the TMJ of Biglycan/Fibromodulin DKO Mice

描述（由申请人提供）：K22奖的建议是在康涅狄格州健康中心（UCHC）牙科医学院的教师过渡阶段的四年。该候选人获得了UCHC的正畸临床证书和博士学位。之后，他在NIDCR完成了三年的博士后培训。他目前是UCHC正畸科的助理教授。该奖项将使候选人能够实现他的直接职业目标，即开发一个成功的R 01补助金申请。这反过来又使他能够实现他的长期目标，即开发一个资金充足的研究计划，研究颅面结构机械载荷应用所涉及的分子和细胞信号通路，并能够将这些基础研究成果转化为临床应用。UCHC的大量共享资源，包括显微断层摄影设施，生物医学成像技术中心和中央电子显微镜设施都可供候选人使用。对候选人的职业发展作出了强有力的机构承诺，包括保护时间和启动费用。此外，候选人还组建了一个由知名科学家组成的咨询委员会，以监督其研究和职业发展进展。该研究项目的目标是通过早期检测和治疗来预防颞下颌关节骨关节炎（TMJ-OA）。该候选人建议使用双双糖链蛋白聚糖/纤维调节蛋白缺陷小鼠作为TMJ-OA模型，以确定TMJ-OA的生物标志物和介质，并评估机械负荷如何影响TMJ-OA的进展。具体目标是1.确定颞下颌关节骨关节炎是否与关节透明软骨骨关节炎具有相似的生物标志物。2.观察骨关节炎时髁突软骨浅关节区细胞凋亡和增殖的变化。3.确定降低机械负荷是否可以抑制TMJ-OA的进展。据估计，美国有1-2百万人患有TMJ-OA。目前，TMJ-OA的治疗方式仅涉及症状的姑息性缓解。进一步了解机械负荷在TMJ-OA进展中的作用以及TMJ-OA特异性生物标志物的开发可能会为TMJ-OA患者带来新的治疗模式。

DESCRIPTION (provided by applicant): The K22 award proposal is for four years of the faculty transition phase at the University of Connecticut Health Center (UCHC) School of Dental Medicine. The candidate received his clinical certificate in Orthodontics and PhD from UCHC. Afterwards, he completed three years of postdoctoral training at the NIDCR. He is currently an Assistant Professor in the Division of Orthodontics at UCHC. This award will enable the candidate to achieve his immediate career objective, which is to develop a successful R01 grant application. This will in turn enable him to achieve his long term goal, which is to develop a well-funded research program that studies the molecular and cellular signaling pathways involved on the application of mechanical loading to craniofacial structures and being able to translate these basic research findings into clinical applications. Substantial shared resources at UCHC, including the Microtomography Facility, the Center for Biomedical Imaging Technology, and the Central Electron Microscope Facility are all available to the candidate. A strong institutional commitment to the candidate's career development in the form of protection of time and start up costs are in place. In addition, the candidate has assembled an advisory committee of well established scientists to monitor his research and career development progress. The goal of the research project is to prevent temporomandibular joint osteoarthritis (TMJ-OA) by detecting and treating it at an early stage. The candidate proposes to use the double biglycan/fibromodulin deficient mice as a model of TMJ-OA to determine biomarkers and mediators of TMJ-OA and to evaluate how mechanical loading affects the progression of TMJ-OA. The specific aims are 1. Determine if osteoarthritis of the temporomandibular joint has similar biomarkers as osteoarthritis of articular hyaline cartilage. 2. Examine changes in apoptosis and proliferation in the superficial articular zone of the mandibular condylar cartilage during osteoarthritis. 3. Determine if decreased mechanical loading can inhibit the progression of TMJ-OA. It is estimated that 1-2 million people in the United States suffer from TMJ-OA. Currently, the treatment modalities for TMJ-OA only involve palliative relief of the symptoms. Greater understanding on the role of mechanical loading in the progression of TMJ-OA and the development of specific biomarkers for TMJ-OA may lead to new treatment modalities for patients who suffer from TMJ-OA.