Mapping the joint-nerve interactome of the knee

绘制膝关节的关节神经相互作用组图

基本信息

  • 批准号:
    10607479
  • 负责人:
  • 金额:
    $ 663.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-23 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

Project Summary Our multidisciplinary team assembles basic and translational researchers with expertise in joint biology and neuroscience, proposing a holistic approach to mapping the sensory innervation of murine and human knee joints. We will use state-of-the-art imaging techniques, combined with transcriptomics 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. Our overarching objective is to precisely describe the sensory innervation of the knee, and the dynamic changes occurring with aging, joint injury, and osteoarthritis (OA). This will provide the Consortium with a rich anatomical and molecular resource to study mechanisms underlying joint pain and guide the development of novel analgesic strategies. Aim 1. Documenting the sensory innervation of the healthy and diseased mouse knee: Anatomical and molecular perspectives. Using fluorescent reporter mice to label nociceptors, C-fiber subsets, and proprioceptors, we will map the anatomical innervation of the mouse knee in (a) naïve mice of different ages; (b) after joint injury; (c) in surgically induced OA. We will use ribbon scanning confocal and clearing-enabled lightsheet microscopy to construct high-resolution 3-D anatomical models of joint innervation. We will backlabel knee-innervating afferents and use spatial transcriptomics to describe their molecular phenotypes compared to other non-knee innervating DRG neurons. Aim 2. Documenting the sensory innervation of the healthy and diseased human knee: Anatomical and molecular perspectives. We will use a unique set of post mortem knee/DRG samples from (1) healthy knees, age 20-40 (n=15/sex); (2) knees from donors over 70 (n=15/sex), in which we anticipate 80-90% to exhibit OA pathology. Knee tissues will be collected in a standardized fashion, including synovium, osteochondral plugs (medial tibial plateau), meniscus, ACL, fat pad, and quadriceps muscle. In each tissue, we will perform (1) histopathology; (2) IHC for sensory innervation; (3) bulk and scRNAseq; (4) spatial transcriptomics. Matched DRGs will be used for bulk RNAseq to identify differentially expressed genes (DEG) between the groups provide information for ligand-receptor analysis. Aim 3. Identifying mediators in the knee synovium that drive disease- associated neuroplasticity. (1) We will reconstruct the cellular interactome between synovial cells and DRG neurons in mouse models of aging, joint injury, and OA using scRNAseq of matched synovium and DRG samples. (2) We will compare patient reports of OA knee pain at the time of TKR to matched synovial histology, including extent of lining hyperplasia, single-cell transcriptional changes, and innervation. Overall, this project will provide the community with comprehensive databases of the neuro-articular environment, which can be mined to (1) undertake mechanistic studies to inhibit pathological neuroplasticity and (2) identify and test new druggable targets. This strategy will pave the way for the development of novel, targeted, non-addictive, and safe analgesic therapeutics for the treatment of joint pain.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Martin K Lotz其他文献

New approach to testing treatments for osteoarthritis: FastOA
骨关节炎治疗测试新方法:快速骨关节炎评估法
  • DOI:
    10.1136/ard-2023-224675
  • 发表时间:
    2024-03-01
  • 期刊:
  • 影响因子:
    20.600
  • 作者:
    David Felson;Martin K Lotz;Yuxuan Jin;Morgan Jones;Jason S Kim;Kurt Spindler
  • 通讯作者:
    Kurt Spindler

Martin K Lotz的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Martin K Lotz', 18)}}的其他基金

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
  • 财政年份:
    2023
  • 资助金额:
    $ 663.31万
  • 项目类别:
High resolution 3D mapping of cellular heterogeneity within multiple types of mineralized tissues
多种矿化组织内细胞异质性的高分辨率 3D 绘图
  • 批准号:
    10705190
  • 财政年份:
    2020
  • 资助金额:
    $ 663.31万
  • 项目类别:
High resolution 3D mapping of cellular heterogeneity within multiple types of mineralized tissues
多种矿化组织内细胞异质性的高分辨率 3D 绘图
  • 批准号:
    10267740
  • 财政年份:
    2020
  • 资助金额:
    $ 663.31万
  • 项目类别:
High resolution 3D mapping of cellular heterogeneity within multiple types of mineralized tissues
多种矿化组织内细胞异质性的高分辨率 3D 绘图
  • 批准号:
    10700252
  • 财政年份:
    2020
  • 资助金额:
    $ 663.31万
  • 项目类别:
High resolution 3D mapping of cellular heterogeneity within multiple types of mineralized tissues
多种矿化组织内细胞异质性的高分辨率 3D 绘图
  • 批准号:
    10816791
  • 财政年份:
    2020
  • 资助金额:
    $ 663.31万
  • 项目类别:
FOXO transcription factors as critical regulators of intervertebral disc aging
FOXO转录因子作为椎间盘老化的关键调节因子
  • 批准号:
    10617735
  • 财政年份:
    2019
  • 资助金额:
    $ 663.31万
  • 项目类别:
FOXO transcription factors as critical regulators of intervertebral disc aging
FOXO转录因子作为椎间盘老化的关键调节因子
  • 批准号:
    10399475
  • 财政年份:
    2019
  • 资助金额:
    $ 663.31万
  • 项目类别:
FoxO transcription factors in joint aging and osteoarthritis pathogenesis
FoxO转录因子在关节衰老和骨关节炎发病机制中的作用
  • 批准号:
    10399471
  • 财政年份:
    2018
  • 资助金额:
    $ 663.31万
  • 项目类别:
KLF4 in joint degradation and regeneration
KLF4 在关节降解和再生中的作用
  • 批准号:
    9927548
  • 财政年份:
    2018
  • 资助金额:
    $ 663.31万
  • 项目类别:
FoxO transcription factors in joint aging and osteoarthritis pathogenesis
FoxO转录因子在关节衰老和骨关节炎发病机制中的作用
  • 批准号:
    9916681
  • 财政年份:
    2018
  • 资助金额:
    $ 663.31万
  • 项目类别:

相似海外基金

How Spinal Afferent Neurons Control Appetite and Thirst
脊髓传入神经元如何控制食欲和口渴
  • 批准号:
    DP220100070
  • 财政年份:
    2023
  • 资助金额:
    $ 663.31万
  • 项目类别:
    Discovery Projects
The mechanisms of the signal transduction from brown adipocytes to afferent neurons and its significance.
棕色脂肪细胞向传入神经元的信号转导机制及其意义。
  • 批准号:
    23K05594
  • 财政年份:
    2023
  • 资助金额:
    $ 663.31万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
  • 批准号:
    10477437
  • 财政年份:
    2021
  • 资助金额:
    $ 663.31万
  • 项目类别:
GPR35 on Vagal Afferent Neurons as a Peripheral Drug Target for Treating Diet-Induced Obesity
迷走神经传入神经元上的 GPR35 作为治疗饮食引起的肥胖的外周药物靶点
  • 批准号:
    10315571
  • 财政年份:
    2021
  • 资助金额:
    $ 663.31万
  • 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
  • 批准号:
    10680037
  • 财政年份:
    2021
  • 资助金额:
    $ 663.31万
  • 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
  • 批准号:
    10654779
  • 财政年份:
    2021
  • 资助金额:
    $ 663.31万
  • 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
  • 批准号:
    10275133
  • 财政年份:
    2021
  • 资助金额:
    $ 663.31万
  • 项目类别:
GPR35 on Vagal Afferent Neurons as a Peripheral Drug Target for Treating Diet-Induced Obesity
迷走神经传入神经元上的 GPR35 作为治疗饮食引起的肥胖的外周药物靶点
  • 批准号:
    10470747
  • 财政年份:
    2021
  • 资助金额:
    $ 663.31万
  • 项目类别:
Roles of mechanosensory ion channels in myenteric intrinsic primary afferent neurons
机械感觉离子通道在肌间固有初级传入神经元中的作用
  • 批准号:
    RGPIN-2014-05517
  • 财政年份:
    2018
  • 资助金额:
    $ 663.31万
  • 项目类别:
    Discovery Grants Program - Individual
Roles of mechanosensory ion channels in myenteric intrinsic primary afferent neurons
机械感觉离子通道在肌间固有初级传入神经元中的作用
  • 批准号:
    RGPIN-2014-05517
  • 财政年份:
    2017
  • 资助金额:
    $ 663.31万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了