Bio-active Nanoparticles and the stimulation of autophagy for improved bone mass

生物活性纳米颗粒和刺激自噬以改善骨量

基本信息

  • 批准号:
    9280823
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-01-01 至 2017-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Objectives: Fractures have serious health consequences including lengthy rehabilitation and the most serious, hip fractures, may cause prolonged or permanent disability and almost always require hospitalization and major surgery. We have engineered a bio-active silica based nanoparticle capable of promoting osteoblast differentiation and mineralization while inhibiting osteoclastogenesis. Furthermore, we have identified a potential key intracellular regulator of the effect in autophagy as well as key signaling pathway in NF-�B. These nanoparticles have the potential to promote new bone formation while simultaneously reducing bone breakdown. Research Plan: Our preliminary studies have identified the cellular process of autophagy as a potential key mechanism by which our nanoparticles differentially alter cell function in osteoblasts and osteoclasts. Autophagy is a highly regulated cellular process that can be induced by various stimuli, such as stress, cytokines, pathogens, aggregated proteins, damaged or surplus organelles that are ultimately degraded. Although only partially understood, autophagy has been linked to controlling cell signaling by targeting the proteasome and restricting inflammation through limiting the IKK/NF-�B pathway. Based on these studies we hypothesize that our engineered nanoparticle represents an agent capable of preventing and/or reversing age- related bone loss by stimulating autophagy in osteoblasts and osteoclasts. Methods: To test our hypothesis we will utilize we will utilize in vitro models of osteoblast and osteoclast differentiation and function to investigate the mechanism(s) by which our nanoparticles alter function. We will investigate the effects of nanoparticle induced autophagy on NF-�B signaling. We will utilize a model of aged induced osteoporosis to determine the effect of our particles in both promoting bone volume and blunting bone loss. Endpoints include a quantitative and qualitative analysis of bone and serum factors while ex vivo studies will address the effects of our nanoparticles individually on osteoblasts and osteoclast in vivo. Clinical Relevance: Fractures have serious health consequences including lengthy rehabilitation, prolonged or permanent disability, and hip fractures almost always require hospitalization with associated major surgery leading to increased morbidity. Prevention of fractures will greatly reduce both the personal and financial burden to veterans relative to post-fracture treatment. The development of "anabolic" agents that can promote the rebuilding of lost bone mass would represent a significant impact on the field and on the treatment of bone disease. No current FDA approved agent is able to achieve this and the benefits of a novel therapeutic agent to supplement, or even replace, current therapies for patients suffering from either naturally occurring or disease associated bone wasting.
描述(由申请人提供): 目的:骨折有严重的健康后果,包括漫长的康复和最严重的髋部骨折,可能会导致长期或永久性残疾,几乎总是需要住院治疗和大手术。我们设计了一种生物活性二氧化硅纳米颗粒,能够促进成骨细胞分化和矿化,同时抑制破骨细胞生成。此外,我们已经确定了一个潜在的关键细胞内调节因子的作用,在自噬以及关键的信号通路NF-β B。这些纳米颗粒有潜力促进新骨形成,同时减少骨分解。 研究计划:我们的初步研究已经确定自噬的细胞过程是一种潜在的关键机制,通过这种机制,我们的纳米颗粒可以不同地改变成骨细胞和破骨细胞的细胞功能。自噬是一种高度调节的细胞过程,可由各种刺激诱导,如应激、细胞因子、病原体、聚集的蛋白质、最终降解的受损或多余的细胞器。虽然只有部分了解,自噬已被链接到控制细胞信号通过靶向蛋白酶体和限制炎症通过限制IKK/NF-β B途径。基于这些研究,我们假设我们的工程纳米颗粒代表能够通过刺激成骨细胞和破骨细胞中的自噬来预防和/或逆转年龄相关的骨丢失的药剂。 研究方法:为了验证我们的假设,我们将利用成骨细胞和破骨细胞分化和功能的体外模型来研究我们的纳米颗粒改变功能的机制。我们将研究纳米颗粒诱导的自噬对NF-β B信号传导的影响。我们将利用老年诱导的骨质疏松症模型来确定我们的颗粒在促进骨体积和钝化骨丢失方面的效果。终点包括骨和血清因子的定量和定性分析,而离体研究将解决我们的纳米颗粒单独对体内成骨细胞和破骨细胞的影响。 临床相关性:骨折具有严重的健康后果,包括漫长的康复、长期或永久残疾,髋部骨折几乎总是需要住院治疗,并伴有相关的大手术,从而导致发病率增加。相对于骨折后治疗,预防骨折将大大减轻退伍军人的个人和经济负担。能够促进丢失的骨量重建的“合成代谢”剂的发展将对该领域和对骨疾病的治疗产生重大影响。目前没有FDA批准的药物能够实现这一点,以及补充或甚至取代目前用于患有天然发生的或疾病相关的骨消耗的患者的治疗的新型治疗剂的益处。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
(3-Amino-phen-yl)methanol.
Synthesis of pH stable, blue light-emitting diode-excited, fluorescent silica nanoparticles and effects on cell behavior.
Bioactive effects of silica nanoparticles on bone cells are size, surface, and composition dependent.
  • DOI:
    10.1016/j.actbio.2018.10.018
  • 发表时间:
    2018-12
  • 期刊:
  • 影响因子:
    9.7
  • 作者:
    Ha, Shin-Woo;Viggeswarapu, Manjula;Habib, Mark M.;Beck, George R., Jr.
  • 通讯作者:
    Beck, George R., Jr.
{{ 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 }}

GEORGE R. BECK其他文献

GEORGE R. BECK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('GEORGE R. BECK', 18)}}的其他基金

Novel strategies to target lung cancer metastasis to bone
针对肺癌骨转移的新策略
  • 批准号:
    10646351
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
Novel strategies to target lung cancer metastasis to bone
针对肺癌骨转移的新策略
  • 批准号:
    10513138
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
ShEEP Request For A Pre-Clinical In-Vivo X-Ray Micro Computed-Tomography Scanner
ShEEP 请求临床前体内 X 射线微型计算机断层扫描仪
  • 批准号:
    10178581
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Bio-active Nanoparticles and the stimulation of autophagy for improved bone mass
生物活性纳米颗粒和刺激自噬以改善骨量
  • 批准号:
    8974367
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
Bio-active Nanoparticles and the stimulation of autophagy for improved bone mass
生物活性纳米颗粒和刺激自噬以改善骨量
  • 批准号:
    8634211
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
Contribution of Phosphate to Inflammatory Bone Loss
磷酸盐对炎性骨质流失的影响
  • 批准号:
    10588936
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Inorganic phosphate regulated proliferation, transformation and tumorigenesis
无机磷酸盐调节增殖、转化和肿瘤发生
  • 批准号:
    8444660
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
Inorganic phosphate regulated proliferation, transformation and tumorigenesis
无机磷酸盐调节增殖、转化和肿瘤发生
  • 批准号:
    7889954
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
Inorganic phosphate regulated proliferation, transformation and tumorigenesis
无机磷酸盐调节增殖、转化和肿瘤发生
  • 批准号:
    8076343
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
Inorganic phosphate regulated proliferation, transformation and tumorigenesis
无机磷酸盐调节增殖、转化和肿瘤发生
  • 批准号:
    8240098
  • 财政年份:
    2010
  • 资助金额:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 项目类别:
    EU-Funded
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:
    --
  • 项目类别:
    Standard Grant
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:
    --
  • 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:
    --
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了