Mechanism of a mimetic peptide CK2.3 on bone formation
模拟肽CK2.3对骨形成的机制
基本信息
- 批准号:9125733
- 负责人:
- 金额:$ 33.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-16 至 2018-11-30
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsAffectAmericanBone DensityBone ResorptionCalvariaCellsClinicDataDevelopmentEventExhibitsFractureGenesGoalsGrowthHealthIn VitroInjection of therapeutic agentLeadMediatingMedicalMineralsMusOsteoblastsOsteoclastsOsteogenesisOsteoporosisPathway interactionsPatientsPeptidesPopulationPublishingQuality of lifeSignal PathwaySignal TransductionTailTestingTherapeuticTherapeutic AgentsWomananalogbasebisphosphonatebonebone cellbone lossbone massbone morphogenetic protein 2bone morphogenetic protein receptor type Ibone morphogenetic protein receptor type IIbone turnovercasein kinase IIcommon treatmentcostdensitydesignin vitro activityin vivomenmineralizationnovelnovel therapeuticsosteoclastogenesispeptidomimeticspreventprotein protein interactionreceptorresearch studyresponsetargeted agenttherapeutic target
项目摘要
DESCRIPTION (provided by applicant): Common treatments for osteoporosis include bisphosphonates, which inhibit osteoclast activity. Newer treatments such as PTH focus on enhancing osteoblast activity. However, due to the crosstalk between osteoblasts and osteoclasts an increase of osteoblast activity may lead to increased osteoclast activity and therefore increased bone turnover. In the clinic this is circumvented by administering bisphosphonates in addition to PTH. A single therapeutic that enhances osteogenesis and decreases osteoclastogenesis and/or osteoclast activity is currently unavailable, but is desperately needed. We propose to determine the mechanism of a new peptide CK2.3 that enhances osteogenesis and decreases osteoclastogenesis and osteoclast activity in vitro and in vivo. Addition of CK2.3 to cells leads to the activation of BMP2 signaling pathways and mineralization. Injection of CK2.3 into calvaria, as well as in the tail vain of mice, increases boe mineral density (BMD). In sharp contrast to BMP2, stimulation of cells with CK2.3 or CK2.3 injection into the tail vain of mice inhibits osteoclast activity in vivo and in vitro. The therapetic CK2.3 stimulates distinct pathways of a powerful growth factor BMP2. CK2.3 is designed to block the interaction between the BMP type Ia receptor (BMPRIA) and Casein Kinase 2 (CK2) leading to activation of specific BMP2 signaling pathways. However, the exact mechanism of the peptide must be explored. A major drawback of the use of BMPs as osteoporosis treatment is the long term affect that causes increased bone turnover. Additionally, BMP2 is known to stimulate osteoclastogenesis. The response of patients to BMP2 shows several side effects and BMP2 is not very effective as a treatment. Based on our published and preliminary data CK2.3 maybe a unique therapeutic that can be used for the treatment of osteoporosis. The goal of this proposal is to determine the mechanism of CK2.3. Even if CK2.3 may not be suitable as a therapeutic for osteoporosis it opens new ways to decipher new pathways and targets for osteoporosis treatment. New therapeutics are desperately needed.
描述(由申请人提供):骨质疏松症的常见治疗方法包括双膦酸盐,其抑制破骨细胞活性。 PTH 等新疗法侧重于增强成骨细胞活性。然而,由于成骨细胞和破骨细胞之间的相互作用,成骨细胞活性的增加可能导致破骨细胞活性增加,从而增加骨转换。在临床上,除了 PTH 之外还可以使用双磷酸盐来避免这种情况。目前尚无法获得增强骨生成并减少破骨细胞生成和/或破骨细胞活性的单一治疗方法,但迫切需要这种治疗方法。我们建议确定一种新肽 CK2.3 的机制,该肽在体外和体内增强成骨作用并减少破骨细胞生成和破骨细胞活性。向细胞中添加 CK2.3 会导致 BMP2 信号通路激活和矿化。将 CK2.3 注射到小鼠的颅骨以及尾部,可增加牛矿物质密度 (BMD)。与BMP2形成鲜明对比的是,用CK2.3刺激细胞或将CK2.3注射到小鼠尾部可抑制体内和体外破骨细胞活性。治疗性 CK2.3 刺激强大的生长因子 BMP2 的不同途径。 CK2.3 旨在阻断 BMP Ia 型受体 (BMPRIA) 和酪蛋白激酶 2 (CK2) 之间的相互作用,从而导致特定 BMP2 信号通路的激活。然而,必须探索肽的确切机制。使用 BMP 治疗骨质疏松症的一个主要缺点是长期影响会导致骨转换增加。此外,已知 BMP2 可以刺激破骨细胞生成。患者对 BMP2 的反应显示出多种副作用,并且 BMP2 作为治疗方法并不是非常有效。根据我们已发表的初步数据,CK2.3可能是一种可用于治疗骨质疏松症的独特疗法。该提案的目标是确定 CK2.3 的机制。即使 CK2.3 可能不适合作为骨质疏松症的治疗方法,它也为破译骨质疏松症治疗的新途径和靶点开辟了新途径。迫切需要新的疗法。
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)
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{{ truncateString('ANJA G NOHE', 18)}}的其他基金
CK2.1, a novel peptide for cartilage repair
CK2.1,一种用于软骨修复的新型肽
- 批准号:
10053849 - 财政年份:2020
- 资助金额:
$ 33.15万 - 项目类别:
CK2.1, a novel peptide for cartilage repair
CK2.1,一种用于软骨修复的新型肽
- 批准号:
10264052 - 财政年份:2020
- 资助金额:
$ 33.15万 - 项目类别:
Mechanism of a mimetic peptide CK2.3 on bone formation
模拟肽CK2.3对骨形成的机制
- 批准号:
8906474 - 财政年份:2013
- 资助金额:
$ 33.15万 - 项目类别:
Mechanism of a mimetic peptide CK2.3 on bone formation
模拟肽CK2.3对骨形成的机制
- 批准号:
8630192 - 财政年份:2013
- 资助金额:
$ 33.15万 - 项目类别:
ROLE OF CK2 AND ENDOGLIN IN BONE MORPHOGENETIC PROTEIN SIGNALING
CK2 和内皮糖蛋白在骨形态发生蛋白信号转导中的作用
- 批准号:
7263673 - 财政年份:2006
- 资助金额:
$ 33.15万 - 项目类别:
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