Mapping the joint-nerve interactome of the knee

绘制膝关节的关节神经相互作用组图

• 批准号: 10861323
• 负责人: Martin K Lotz
• 金额: $ 122.35万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-13 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10861323
• 关键词: ATAC-seq; Address; Age; Antibodies; Atlases; Bilateral; Blood Vessels; Cells; Chronic low back pain; Connective Tissue; Degenerative polyarthritis; Disease; Facet joint structure; Female; Funding; Gene Expression Profile; Generations; Genetic Transcription; Goals; Human; Intervertebral disc structure; Joints; Knee; Knee Osteoarthritis; Knee joint; Low Back Pain; Maps; Methods; Molecular; Molecular Analysis; Muscle; Nerve; Neurons; Nociceptors; Pain; Parents; Pathologic; Phase; Population; Price; Proprioceptor; Proteins; Research; Research Personnel; Resolution; Sensory; Small Nuclear RNA; Spatial Distribution; Spinal Ganglia; Structure; Temporomandibular Joint; Texas; Tissue Banks; Tissue Donors; Tissues; Universities; Vertebral column; Work; aged; axon guidance; cell type; chronic pain; epigenome; gene regulatory network; human old age (65+); insight; intervertebral disk degeneration; knee pain; male; mouse model; nerve supply; neural; neurotrophic factor; novel; parent grant; programs; therapeutic target; three-dimensional modeling; tissue degeneration; transcriptome; transcriptome sequencing; transcriptomics; vertebra body

ABSTRACT This supplement addresses are proposed studies are in the context of spine tissue damage and chronic low back pain (LBP). The goals of the parent grant are to construct 3D models of the sensory innervation of the knee, compose a cell atlas in which knee afferents are transcriptionally profiled at a single cell resolution, and document the nerve-joint cell interactome at the transcriptional level. The supplement substantially expands the scope and potential impact of the parent program by examining mechanisms of intervertebral disc (IVD) degeneration (IDD), facet joint (FJ) osteoarthritis (OA) and the interaction of these tissues with neurons in the generation of low back pain. The inclusion of the FJ also extends the portfolio of joints (knee and temporomandibular joints) that are currently being investigated in the RE-JOIN consortium. The team includes investigators at Rush University (PI Dr. Anne-Marie Malfait) and Scripps Research (PI Dr. Martin Lotz) in the funded UC2 project for the analysis of knee joints and adds new methods for the analysis of IVD and FC degeneration and the team at the University of Texas, Dallas (PI Dr. Theodore Price) adds expertise in the analysis of dorsal root ganglia (DRG). The team at Scripps has a long-standing program on mechanisms of knee OA and performed prior work on mechanisms of IDD, using mouse models and human spines. Omics analyses were applied to define cell populations and their gene regulatory networks in healthy and degenerated IVD. The team at Rush is a leader in the analysis of pain mechanisms in OA and has expertise in the analysis of neural structures in knee joints and in the analysis of chronic pain mechanisms. The two teams are working together in the funded RE-JOIN project about knee pain. Our unique approach is to examine spine and knee tissues from the same young healthy and older donors with OA and IDD for innervation, transcriptome and epigenome at tissue, single cell, and spatial levels. The integrative analysis of neural and connective tissue changes during IDD will reveal critical interactions that promote tissue damage and pain.

摘要 本补充地址是建议的研究是在脊柱组织损伤和慢性低 背痛（LBP）。父母资助的目标是构建膝关节感觉神经支配的3D模型， 组成一个细胞图谱，其中膝传入神经以单细胞分辨率进行转录分析，并记录 神经-关节细胞相互作用组在转录水平。 该补充大大扩大了范围和潜在影响的母计划，通过审查 椎间盘（IVD）退变（IDD）、小关节（FJ）骨关节炎（OA）和 这些组织与神经元的相互作用在腰痛的产生。FJ的加入也扩大了 目前正在RE-JOIN中研究的关节组合（膝关节和颞下颌关节） 财团 该小组包括拉什大学（PI博士安妮玛丽Malfait）和斯克里普斯研究（PI博士。 Martin Lotz）在用于膝关节分析的UC 2资助项目中， IVD和FC变性和团队在得克萨斯大学，达拉斯（PI博士西奥多价格）增加专业知识 背根神经节（DRG）的分析。斯克里普斯的团队有一个长期的机制计划 的膝关节OA和IDD的机制进行了前期工作，使用小鼠模型和人类脊柱。组学 分析应用于定义健康和退化的细胞群体及其基因调控网络， IVD。Rush的团队是OA疼痛机制分析的领导者，并具有分析方面的专业知识 在膝关节神经结构和慢性疼痛机制的分析。两支队伍正在努力 一起参加了一个关于膝盖疼痛的RE-JOIN项目。我们独特的方法是检查脊柱和膝盖 来自相同的年轻健康和患有OA和IDD的老年供体的组织用于神经支配、转录组和 表观基因组在组织、单细胞和空间水平。神经与结缔组织的综合分析 IDD期间的变化将揭示促进组织损伤和疼痛的关键相互作用。