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
- 来源:
- 关键词:AcuteAddressAdultAge-Related Bone LossAgingAnabolic AgentsArtificial nanoparticlesAutophagocytosisAutophagosomeBindingBiologicalBiomechanicsBone DensityBone DiseasesCell Culture TechniquesCell physiologyCellsDevelopmentDevicesDiseaseElementsEndocytosisEngineeringExtracellular MatrixExtracellular StructureFDA approvedFormulationFractureGenetic studyHealthHip FracturesHospitalizationIn VitroIndividualInflammationKnockout MiceLinkLysosomesMediatingMethodsModelingMolecularMorbidity - disease rateMusNF-kappa BNanotechnologyOperative Surgical ProceduresOrganellesOsteoblastsOsteoclastsOsteogenesisOsteoporosisPathway interactionsPatientsPhenotypePhosphotransferasesPreventionPropertyProteinsPublishingRehabilitation therapyResearchRoleSerumSignal PathwaySignal TransductionSilicon DioxideStimulusStressTestingTherapeutic AgentsTherapeutic UsesTissuesVeteransage relatedagedbasebiomaterial compatibilitybonebone lossbone massbone metabolismbone turnoverclinically relevantcytokinedisabilityimprovedin vitro Modelin vivomineralizationmouse modelmulticatalytic endopeptidase complexmultidisciplinarynanomaterialsnanoparticlenanoscalenew therapeutic targetnovelnovel therapeuticsosteoblast differentiationosteoclastogenesisparticlepathogenpreventprotein aggregateprotein degradationpublic health relevancerepairedresponseskeletalskeletal disorderwasting
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):
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.
- DOI:10.1107/s1600536811029163
- 发表时间:2011-08-01
- 期刊:
- 影响因子:0
- 作者:Betz R;Gerber T;Hosten E
- 通讯作者:Hosten E
Synthesis of pH stable, blue light-emitting diode-excited, fluorescent silica nanoparticles and effects on cell behavior.
- DOI:10.2147/ijn.s139562
- 发表时间:2017
- 期刊:
- 影响因子:8
- 作者:Ha SW;Lee JK;Beck GR Jr
- 通讯作者:Beck GR Jr
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:
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