Biomolecular and Cellular Mechanisms of Diabetic Skeletal Fragility

糖尿病骨骼脆性的生物分子和细胞机制

• 批准号: 10439180
• 负责人: Lamya Karim
• 金额: $ 10.03万
• 依托单位: UNIVERSITY OF MASSACHUSETTS DARTMOUTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-26 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10439180
• 关键词: Advanced Glycosylation End Products; Biomechanics; Biomedical Engineering; Bone Matrix; COVID-19 pandemic; Cell Culture Techniques; Clinical; Clinical Management; Diabetes Mellitus; Fracture; Gene Expression; Goals; Healthcare; Hyperglycemia; Institution; Israel; Lead; Massachusetts; Measurement; Medical center; Mentored Research Scientist Development Award; Mentors; Methods; Molecular Biology; Molecular Biology Techniques; Non-Insulin-Dependent Diabetes Mellitus; Orthopedics; Osteocytes; Porosity; Prevention; Public Health; Research; Resources; Risk Assessment; Technology; Time; Training; Type 2 diabetic; Universities; Vocational Guidance; Work; diabetic; diabetic patient; fracture risk; glycation; high resolution imaging; improved; non-diabetic; professor; skeletal; skills; tissue culture

Project Summary/Abstract This proposal includes a supplementary research plan that allows for successful completion of the PI’s original 5-year K01 project. The PI is currently an Assistant Professor in the Department of Bioengineering at the University of Massachusetts Dartmouth and a formal Research Collaborator at the Center for Advanced Orthopaedic Studies (CAOS) at Beth Israel Deaconess Medical Center (BIDMC). She is well supported by her institution and devotes 75% effort to this project. The PI has mentors and collaborators with a wide array of expertise to help her conduct her work and offer career guidance during this project. Her mentors and collaborators have expertise in biomechanics, clinical issues in diabetes, cell and tissue culture methods, high- resolution imaging, and molecular biology techniques. This project focuses on the causes of skeletal fragility in type 2 diabetes, which are largely unknown. Deficits in bone matrix via the accumulation of advanced glycation end-products and/or microarchitecture have been suggested to be potential mechanisms. The overall goal of this project is to determine the underlying biomolecular and cellular mechanisms of diabetic skeletal fragility with a specific focus during this supplemental 6-month period to successfully complete two of her original aims. These two aims are: A) to determine the contribution of advanced glycation end-products, microdamage, and cortical porosity to diabetic skeletal fragility, and B) to determine the effect of hyperglycemia and non-enzymatic glycation on osteocyte activity. The candidate has already trained in several brand-new skills including measurement of gene expression, cell and tissue culture methods, and other molecular biology related technologies as part of her originally awarded K01 project. This K01 supplemental proposal will provide her with additional time and resources (needed due to COVID-19 pandemic-related research hindrances) to successfully achieve these goals.

项目概要/摘要 该提案包括一个补充研究计划，允许 PI 的原始研究计划成功完成 为期5年的K01项目。 PI现为北京大学生物工程系助理教授 马萨诸塞大学达特茅斯分校和高级中心的正式研究合作者 贝斯以色列女执事医疗中心 (BIDMC) 的骨科研究 (CAOS)。她得到了她的大力支持 机构并为该项目投入了 75% 的精力。 PI 拥有广泛领域的导师和合作者 专业知识帮助她开展工作并在该项目期间提供职业指导。她的导师和 合作者拥有生物力学、糖尿病临床问题、细胞和组织培养方法、高 分辨率成像和分子生物学技术。该项目重点研究骨骼脆弱的原因 2 型糖尿病，目前尚不清楚。晚期糖基化的积累导致骨基质缺陷 最终产品和/或微架构被认为是潜在的机制。总体目标为 该项目旨在确定糖尿病骨骼脆性的潜在生物分子和细胞机制 在这六个月的补充期间，她的具体重点是成功完成她最初的两个目标。这些 两个目标是：A) 确定晚期糖基化终产物、微损伤和皮质的贡献 孔隙度对糖尿病骨骼脆性的影响，B) 确定高血糖和非酶糖化的影响 关于骨细胞活性。候选人已经接受过多项全新技能的培训，包括测量 基因表达、细胞和组织培养方法以及其他分子生物学相关技术作为 她最初获得的K01项目。这个K01补充提案将为她提供额外的时间和 成功实现这些目标所需的资源（由于与 COVID-19 大流行相关的研究障碍而需要） 目标。

项目成果

Bone microarchitecture, biomechanical properties, and advanced glycation end-products in the proximal femur of adults with type 2 diabetes.

• DOI: 10.1016/j.bone.2018.05.030
• 发表时间: 2018-09
• 期刊: Bone
• 影响因子: 4.1
• 作者: Karim L;Moulton J;Van Vliet M;Velie K;Robbins A;Malekipour F;Abdeen A;Ayres D;Bouxsein ML
• 通讯作者: Bouxsein ML

Fracture behavior of human cortical bone: Role of advanced glycation end-products and microstructural features.

• DOI: 10.1016/j.jbiomech.2021.110600
• 发表时间: 2021-07
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: E. Maghami;Timothy O. Josephson;Jason P. Moore;T. Rezaee;T. Freeman;L. Karim;A. Najafi

Accumulation of fluorescent advanced glycation end products and carboxymethyl-lysine in human cortical and trabecular bone.

• DOI: 10.1016/j.bonr.2022.101634
• 发表时间: 2022-12
• 期刊: BONE REPORTS
• 影响因子: 2.5
• 作者: Vaidya, Rachana;Rezaee, Taraneh;Edwards, Tianna;Bender, Richard;Vickneswaran, Arune;Chalivendra, Vijaya;Karim, Lamya
• 通讯作者: Karim, Lamya