Osteoarthritis and Knee Joint Pain
骨关节炎和膝关节疼痛
基本信息
- 批准号:10549317
- 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:2014-10-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAfferent NeuronsAgeAnalgesicsAnimal ModelAntineoplastic AgentsAreaArthralgiaArthritisAstrocytesAutomobile DrivingBehavioralCellsChronicClinicalClinical TrialsDegenerative polyarthritisDiseaseEconomic BurdenFamilyFrequenciesGenesGenomicsGoalsHealth systemHumanHyaluronic AcidIncidenceIndividualInjuryIntra-Articular InjectionsJointsKDR geneKnee jointKnowledgeLettersLifeLigandsMacular degenerationMalignant NeoplasmsMedialMedicalMedical AssistanceMilitary PersonnelModelingMolecularMorbidity - disease rateMusNeuronal PlasticityNeuronsNociceptionOperative Surgical ProceduresPGF genePainPain FreePain OriginPathologicPathologic NeovascularizationPathologyPathway interactionsPatientsPeripheralPharmaceutical PreparationsPlayPopulationProsthesisPublic HealthQuality of lifeReceptor Protein-Tyrosine KinasesReplacement ArthroplastyReportingResearchRiskRoleSafetySeveritiesSignal TransductionSpinalSpinal CordSymptomsSynaptic TransmissionTestingTherapeutic EffectTimeTissue SampleTissuesTraumaTraumatic ArthropathyTreatment CostUnited States Food and Drug AdministrationVEGFA geneVEGFR inhibitionVascular Endothelial Growth Factor BVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth FactorsVertebral columnVeteransVirusWorkZD-6474blood vessel developmentcartilage degradationcartilage regenerationcontrolled releasecostcrosslinkdisabilitydrug efficacydrug testinggender differenceglial activationhealth managementindustry partnerinhibitornovel strategiesosteoarthritis painpain reductionpharmacologicpre-clinicalpreventreceptorresponsesmall moleculesmall molecule inhibitortechnology platformtissue regenerationtransmission process
项目摘要
ABSTRACT:
Osteoarthritis (OA), commonly referred as arthritis, causing painful joints, is among the most common chronic
conditions among veterans. Indeed, the condition is much worse among veterans than non-veterans; one of
every four veterans lives with a serious arthritic condition and individuals over age 40 are twice as likely to
develop arthritis after returning to civilian life. Osteoarthritic symptom, pain, is the key reason to seek medical
assistance, yet there is no effective way to relieve OA-induced pain.
Despite the major negative impact that severe pain in chronic OA has on quality of life and health care
management, we only poorly understand origins of pain in OA, the molecular mechanisms driving the
pathology, and the way to effectively cure OA. Many cases eventually require joint replacement with a
prosthesis which is costly, and the limited functional life of prostheses (~10 y) can make a second replacement
necessary. These factors increase both the overall cost of treatment and the risk for associated morbidity.
Significantly, surgical procedures to address the condition typically do not result in a pain-free cure.
Our central hypothesis is that activation of Flt1 (vascular endothelial growth factor receptor-1) is the major
driver of joint pain transmission by plasticity of peripheral (sensory neurons) and central glial activation; Flk1
(vascular endothelial growth factor receptor-2) is primarily responsible for cartilage degeneration during the OA
progression, thus, simultaneous inhibition of Flt1 and Flk1 by pazopanib, an FDA-approved small molecule
anti-cancer drug, will act as an ideal OA disease-modifying drug (OADMD) with immediate reduction of joint
pain and gradually cartilage regeneration. The findings of our proposed research will take the field of OA
research a giant step forward: in the short term, by increasing our mechanistic understanding of the causes
and progression of OA, and by developing a novel strategy for treating OA and joint pain effectively and safely
in our pre-clinical OA animal model; and, in the longer term, by providing a rationale for clinical trials to test
pazopanib to treat OA patients.
抽象的:
骨关节炎 (OA),通常称为关节炎,会导致关节疼痛,是最常见的慢性疾病之一
退伍军人之间的状况。事实上,退伍军人的情况比非退伍军人要糟糕得多。之一
每四名退伍军人中就有一名患有严重的关节炎,而 40 岁以上的退伍军人罹患严重关节炎的可能性是其两倍
返回平民生活后患关节炎。骨关节炎症状、疼痛是就医的主要原因
但目前还没有有效的方法来缓解 OA 引起的疼痛。
尽管慢性骨关节炎的剧烈疼痛对生活质量和医疗保健产生重大负面影响
在管理方面,我们对 OA 疼痛的起源、驱动疼痛的分子机制知之甚少。
病理学,以及有效治疗OA的方法。许多病例最终需要关节置换术
假体价格昂贵,而且假体的功能寿命有限(~10年)可以进行第二次更换
必要的。这些因素增加了治疗的总体成本和相关发病的风险。
值得注意的是,针对这种情况的外科手术通常不会带来无痛治愈。
我们的中心假设是 Flt1(血管内皮生长因子受体-1)的激活是主要的
通过外周(感觉神经元)的可塑性和中枢神经胶质的激活驱动关节疼痛传递;弗尔克1
(血管内皮生长因子受体-2)主要负责 OA 期间的软骨退化
因此,帕唑帕尼(FDA 批准的小分子)同时抑制 Flt1 和 Flk1
抗癌药物,将作为理想的 OA 疾病缓解药物 (OADMD),可立即减少关节损伤
疼痛并逐渐软骨再生。我们提议的研究结果将涉及 OA 领域
研究向前迈出了一大步:在短期内,通过增加我们对原因的机械理解
以及 OA 的进展,并开发一种有效、安全地治疗 OA 和关节疼痛的新策略
在我们的临床前 OA 动物模型中;从长远来看,通过为临床试验提供理由来测试
帕唑帕尼用于治疗 OA 患者。
项目成果
期刊论文数量(62)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
MMP13 is a critical target gene during the progression of osteoarthritis.
- DOI:10.1186/ar4133
- 发表时间:2013-01-08
- 期刊:
- 影响因子:4.9
- 作者:Wang M;Sampson ER;Jin H;Li J;Ke QH;Im HJ;Chen D
- 通讯作者:Chen D
Osteoarthritis: toward a comprehensive understanding of pathological mechanism.
- DOI:10.1038/boneres.2016.44
- 发表时间:2017
- 期刊:
- 影响因子:12.7
- 作者:Chen D;Shen J;Zhao W;Wang T;Han L;Hamilton JL;Im HJ
- 通讯作者:Im HJ
Biological Effects of the Herbal Plant-Derived Phytoestrogen Bavachin in Primary Rat Chondrocytes.
- DOI:10.1248/bpb.b15-00198
- 发表时间:2015-08
- 期刊:
- 影响因子:2
- 作者:Gyeong-Je Lee;In-A Cho;Kyeong-Rok Kang;Do Kyung Kim;H. Sohn;J. You;Ji-Su Oh;Yo-Seob Seo;
- 通讯作者:Gyeong-Je Lee;In-A Cho;Kyeong-Rok Kang;Do Kyung Kim;H. Sohn;J. You;Ji-Su Oh;Yo-Seob Seo;
Increased expression of the Akt/PKB inhibitor TRB3 in osteoarthritic chondrocytes inhibits insulin-like growth factor 1-mediated cell survival and proteoglycan synthesis.
- DOI:10.1002/art.24225
- 发表时间:2009-02
- 期刊:
- 影响因子:0
- 作者:Cravero, John D.;Carlson, Cathy S.;Im, Hee-Jeong;Yammani, Raghunatha R.;Long, David;Loeser, Richard F.
- 通讯作者:Loeser, Richard F.
Licochalcone-A induces intrinsic and extrinsic apoptosis via ERK1/2 and p38 phosphorylation-mediated TRAIL expression in head and neck squamous carcinoma FaDu cells.
- DOI:10.1016/j.fct.2014.12.013
- 发表时间:2015-03
- 期刊:
- 影响因子:0
- 作者:Park MR;Kim SG;Cho IA;Oh D;Kang KR;Lee SY;Moon SM;Cho SS;Yoon G;Kim CS;Oh JS;You JS;Kim DK;Seo YS;Im HJ;Kim JS
- 通讯作者:Kim JS
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Hee-Jeong Im Sampen其他文献
Hee-Jeong Im Sampen的其他文献
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{{ truncateString('Hee-Jeong Im Sampen', 18)}}的其他基金
BLRD Research Career Scientist Award Application.
BLRD 研究职业科学家奖申请。
- 批准号:
10366566 - 财政年份:2021
- 资助金额:
-- - 项目类别:
BLRD Research Career Scientist Award Application.
BLRD 研究职业科学家奖申请。
- 批准号:
10513327 - 财政年份:2021
- 资助金额:
-- - 项目类别:
ShEEP Request for IVIS SPECTRUMCT, 2D and 3D Optical In Vivo Tomography System.
ShEEP 请求 IVIS SPECTRUMCT、2D 和 3D 光学体内断层扫描系统。
- 批准号:
9907225 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Pathological Role of bFGF in Human Adult Articular Cartilage
bFGF 在人类成人关节软骨中的病理作用
- 批准号:
7847270 - 财政年份:2009
- 资助金额:
-- - 项目类别:
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