Accelerated Osteoarthritis in the TMJ of Biglycan/Fibromodulin DKO Mice

双糖链蛋白聚糖/纤维调节蛋白 DKO 小鼠颞下颌关节加速骨关节炎

• 批准号: 7630507
• 负责人: Sunil Wadhwa
• 金额: $ 13.5万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7630507
• 关键词: Advisory Committees; Affect; Age; Anatomy; Apoptosis; Apoptotic; Applications Grants; Architecture; Award; Basic Science; Biological Markers; Cartilage; Cell Line; Cells; Chondrocytes; Clinical; Collagen Fibril; Collagen Type II; Complex; Connecticut; Connective Tissue; Degenerative polyarthritis; Dental Schools; Development; Diagnosis; Disease; Doctor of Philosophy; Electron Microscope; Epiphysial cartilage; Faculty; Fibrocartilages; Funding; Goals; Health; Hyaline Cartilage; Imaging Techniques; Imaging technology; Immunofluorescence Immunologic; Immunohistochemistry; Joints; K22 Award; Knee; Knee Osteoarthritis; Knowledge; Label; Lead; Leucine; Long-Term Effects; Mandible; Measures; Mechanics; Mediator of activation protein; Medicine; Modality; Modeling; Molecular; Monitor; Mus; National Institute of Dental and Craniofacial Research; Orthodontics; Patients; Phase Transition; Phenotype; Population; Property; Proteoglycan; Research; Research Personnel; Research Project Grants; Resource Sharing; Role; Scientist; Severities; Signal Pathway; Soft Diet; Staging; Structure; Symptoms; Temporomandibular Joint; Temporomandibular Joint Disorders; Temporomandibular joint osteoarthritis; Testing; Time; Translating; Transmission Electron Microscopy; United States; Universities; Western Blotting; Work; aged; biglycan; bioimaging; bone; career; career development; clinical application; condylar cartilage; cost; craniofacial; fibromodulin; innovation; male; mouse model; palliative; post-doctoral training; prevent; professor; programs

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.

描述（由申请人提供）：K22奖励提案是在康涅狄格大学卫生中心（UCHC）牙科医学学院的教师过渡阶段四年的。候选人获得了UCHC的牙齿牙和博士学位的临床证书。之后，他在NIDCR完成了三年的博士后培训。他目前是UCHC矫正部门的助理教授。该奖项将使候选人能够实现他的直接职业目标，即制定成功的R01赠款申请。反过来，这将使他能够实现自己的长期目标，即制定资金良好的研究计划，该计划研究分子和细胞信号传导途径涉及在机械载荷在颅面结构中的应用上，并能够将这些基础研究结果转化为临床应用。候选人可以使用UCHC的大量共享资源，包括微观学设施，生物医学成像技术中心和中央电子显微镜设施。以保护时间和启动成本的形式对候选人的职业发展做出了强有力的承诺。此外，候选人还组建了一个成熟的科学家咨询委员会，以监视他的研究和职业发展进步。研究项目的目的是通过在早期检测和治疗颞下颌关节骨关节炎（TMJ-OA）。候选人建议使用双重大型群/纤维蛋白缺乏小鼠作为TMJ-OA的模型，以确定TMJ-OA的生物标志物和介体，并评估机械负荷如何影响TMJ-OA的进展。具体目的是1。确定颞下颌关节的骨关节炎是否具有与关节透明软骨的骨关节炎相似的生物标志物。 2。检查骨关节炎期间下颌骨软骨浅表关节区域中凋亡和增殖的变化。 3。确定机械载荷减少是否可以抑制TMJ-OA的进展。据估计，美国有1-200万人患有TMJ-OA。目前，TMJ-OA的治疗方式仅涉及姑息性症状的缓解。对机械负荷在TMJ-OA进展中的作用以及TMJ-OA的特定生物标志物的发展可能会导致患有TMJ-OA的患者的新治疗方式。

项目成果

Altered functional loading causes differential effects in the subchondral bone and condylar cartilage in the temporomandibular joint from young mice.

• DOI: 10.1016/j.joca.2008.05.021
• 发表时间: 2009-03
• 期刊: Osteoarthritis and cartilage
• 影响因子: 7
• 作者: Chen J;Sorensen KP;Gupta T;Kilts T;Young M;Wadhwa S
• 通讯作者: Wadhwa S

Sex differences in chondrocyte maturation in the mandibular condyle from a decreased occlusal loading model.

• DOI: 10.1007/s00223-011-9498-9
• 发表时间: 2011-08
• 期刊: CALCIFIED TISSUE INTERNATIONAL
• 影响因子: 4.2
• 作者: Chen, J.;Sobue, T.;Utreja, A.;Kalajzic, Z.;Xu, M.;Kilts, T.;Young, M.;Wadhwa, S.
• 通讯作者: Wadhwa, S.

Murine TMJ loading causes increased proliferation and chondrocyte maturation.

• DOI: 10.1177/0022034510390810
• 发表时间: 2011-04
• 期刊: Journal of dental research
• 影响因子: 7.6
• 作者: Sobue T;Yeh WC;Chhibber A;Utreja A;Diaz-Doran V;Adams D;Kalajzic Z;Chen J;Wadhwa S
• 通讯作者: Wadhwa S

Analysis of microarchitectural changes in a mouse temporomandibular joint osteoarthritis model.

• DOI: 10.1016/j.archoralbio.2009.10.001
• 发表时间: 2009-12
• 期刊: ARCHIVES OF ORAL BIOLOGY
• 影响因子: 3
• 作者: Chen, J.;Gupta, T.;Barasz, J. A.;Kalajzic, Z.;Yeh, W. -C.;Drissi, H.;Hand, A. R.;Wadhwa, S.
• 通讯作者: Wadhwa, S.

Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice.

• DOI: 10.1016/j.bone.2006.11.003
• 发表时间: 2007-04
• 期刊: Bone
• 影响因子: 4.1
• 作者: S. Wadhwa;Y. Bi;A. T. Ortiz;M. Embree;T. Kilts;R. Iozzo;L. Opperman;M. Young