Pulp fibroblast-mediated inferior alveolar nerve regeneration

牙髓成纤维细胞介导的下牙槽神经再生

基本信息

  • 批准号:
    9979112
  • 负责人:
  • 金额:
    $ 15.99万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-06-01 至 2022-05-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract The dental pulp is composed of a supporting reticular matrix containing blood vessels, nerves, stromal fibroblasts and few specific stem cells. Regenerative medicine has focused on the dental pulp stem cell as a ready source of multipotential adult stem cells. However, the dental pulp fibroblast also may provide important cues for the functioning dental pulp. Included is the dental pulp fibroblast’s support of nerve repair. This project adopts an innovative and alternative approach to regenerative sciences by leveraging the neurotrophic features of dental pulp fibroblasts, potentially for nerve regeneration therapies. Here we explore ways of enhancing this neurotropic function of pulp fibroblasts via a novel C5L2 pathway involving p38 map kinase (p38) signaling. We recently studied the complement C5a receptor (C5aR) as one of the initial events that control the brain-derived neurotrophic factor (BDNF) secretion. This resultant BDNF secretion induces neurite outgrowth towards the injury site. Whereas C5a is known to interact with its G-coupled protein receptor C5aR, another controversial C5a receptor has been cloned. The C5L2 was considered as a non-functional decoy receptor of C5a signaling, thus has received much less attention than C5aR. Preliminary data demonstrate that C5L2 inhibition by siRNA significantly increases the pulp fibroblast-mediated BDNF secretion and neurite outgrowth. We provide further evidence that p38 plays a key role in the pulp fibroblast-mediated BDNF modulation. Based on our observations, we hypothesize that pulp fibroblasts enhance nerve regeneration by a paracrine function of secreted neurotrophic factors via the C5L2 and p38 pathways. In this proposal, we will characterize the mechanisms of C5L2 action in the pulp fibroblast-mediated nerve outgrowth in vitro. We will use an axon investigation system device (AXIS) to identify the interaction with C5L2 and p38, and whether C5L2 function is dependent or independent of C5a/C5aR. We will further determine, in vivo, whether C5L2 acts on pulp fibroblast functions to control IAN regeneration using our mouse IAN regeneration model by transplantation of the C5L2-silenced pulp fibroblasts. In our follow-on R01, we will investigate how pulp fibroblast-mediated nerve regeneration and C5L2 signaling impact functional plasticity: (a) whether the gene knockout approaches demonstrate nerve regenerative potential using in vivo IAN regeneration model, (b) whether the transplantation of engineered pulp fibroblasts and dental pulp stem cells that constitutively express and BDNF into the IAN denervation model can enhance nerve regeneration, (c) the consequence of nerve regeneration regarding pulp and dentin healing, and (d) the consequence of nerve regeneration regarding a behavioral (i.e., pain) effect. The results obtained from this project will shed new light onto cellular and molecular events which orchestrate initial steps of nerve regeneration by linking the neurite outgrowth to pulp fibroblast function through C5L2 and p38 pathways. These studies will provide the basis for future potential therapeutic interventions of nerve repair and vital tooth preservation.
项目总结/摘要 牙髓是由含有血管、神经、基质和纤维的网状基质构成的 成纤维细胞和很少的特异性干细胞。再生医学已经将牙髓干细胞作为一种 多能成体干细胞的现成来源。然而,牙髓成纤维细胞也可以提供重要的 牙髓功能的线索包括牙髓成纤维细胞对神经修复的支持。这个项目 通过利用神经营养功能,采用创新和替代方法进行再生科学 牙髓成纤维细胞,潜在的神经再生疗法。在这里,我们探讨如何提高这一点 牙髓成纤维细胞的神经营养功能通过一种新的C5 L2途径,涉及p38映射激酶(p38)信号。我们 最近研究了补体C5 a受体(C5 aR)作为控制脑源性 神经营养因子(BDNF)分泌。这种合成的BDNF分泌诱导神经突向轴突生长。 受伤部位。尽管已知C5 a与其G偶联蛋白受体C5 aR相互作用,另一个有争议的 C5 a受体已被克隆。C5 L2被认为是C5 a信号传导的非功能性诱饵受体, 因此,它受到的关注远低于C5 aR。初步数据表明,通过siRNA抑制C5 L2 显着增加牙髓成纤维细胞介导的脑源性神经营养因子分泌和神经突生长。我们进一步提供 p38在牙髓成纤维细胞介导的BDNF调节中起关键作用的证据。根据我们的观察, 我们假设牙髓成纤维细胞通过分泌的神经元的旁分泌功能促进神经再生, 神经营养因子通过C5 L2和p38途径。在本提案中,我们将描述 C5 L2在牙髓成纤维细胞介导的神经生长中的作用我们将使用轴突调查系统 设备(AXIS),以确定与C5 L2和p38的相互作用,以及C5 L2功能是否依赖或 与C5 a/C5 aR无关。我们将进一步确定,在体内,C5 L2是否作用于牙髓成纤维细胞功能, 通过移植C5 L2沉默的牙髓,使用我们的小鼠IAN再生模型控制IAN再生 成纤维细胞在我们后续的R 01中,我们将研究牙髓成纤维细胞介导的神经再生和C5 L2 信号传导影响功能可塑性:(a)基因敲除方法是否证明神经再生 可能使用体内IAN再生模型,(B)是否移植工程化牙髓成纤维细胞 而组成性表达BDNF的牙髓干细胞进入IAN去神经模型, 神经再生,(c)神经再生对牙髓和牙本质愈合的影响,以及(d) 关于行为的神经再生的结果(即,疼痛)效果。由此获得的结果 该项目将为细胞和分子事件提供新的线索,这些事件协调了神经再生的初始步骤 通过C5 L2和p38通路将神经突生长与牙髓成纤维细胞功能联系起来。这些研究将 为未来神经修复和活齿保存的潜在治疗干预提供基础。

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 }}

Seung Chung其他文献

Seung Chung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('Seung Chung', 18)}}的其他基金

Role of complement receptor C5L2 in reparative dentinogenesis
补体受体 C5L2 在修复性牙本质发生中的作用
  • 批准号:
    10596148
  • 财政年份:
    2022
  • 资助金额:
    $ 15.99万
  • 项目类别:
Role of complement receptor C5L2 in reparative dentinogenesis
补体受体 C5L2 在修复性牙本质发生中的作用
  • 批准号:
    10445496
  • 财政年份:
    2022
  • 资助金额:
    $ 15.99万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 15.99万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 15.99万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 15.99万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 15.99万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 15.99万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 15.99万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 15.99万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 15.99万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 15.99万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 15.99万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了