New craniofacial bone engineering through miR-23-27-24 cluster mediated osteogenic-angiogenic coupling

通过miR-23-27-24簇介导的成骨-血管生成耦合的新颅面骨工程

基本信息

  • 批准号:
    10252923
  • 负责人:
  • 金额:
    $ 32.49万
  • 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:
    2020-09-03 至 2025-05-31
  • 项目状态:
    未结题

项目摘要

Blood vessels affect all aspects of bone physiology, including mineral growth during new bone formation. To engineer bone as a vascularized tissue we have now focused on microRNAs as molecular engineering tools because of their ability to reversibly target multiple regulatory networks. Recent studies from our and other laboratories have demonstrated that miRNAs promote bone lineage differentiation and new bone formation through WNT, BMP, and Notch signaling pathways and also control bone resorption. In our quest for novel therapeutics that promote coupled bone remodeling and angiogenesis for the treatment of large bone defects we have here identified the miR-27~23~24 microRNA cluster as a highly promising miRNA candidate reagent. Our preliminary analysis revealed multiple miR-23 and miR-27 binding sites on the untranslated region (UTR) of the Wnt antagonist Sfrp1 and Nlk 3’, which in conjunction with miR-24 binding sites on the UTR of the angiogenesis inhibitors BIM and SEMA4A demonstrate the potential of the miR-27-23-24 microRNA cluster for coupled osteogenic and angiogenic molecular engineering strategies. In preliminary studies, we have demonstrated that miR-23-27-24 cluster member expression was greatly reduced in inflammatory tissues. Conversely, miR-27 mimic treatment of diseased periodontal tissues with severe vertical bone defects resulted in unexpectedly extensive new bone formation as evidenced by 80% complete restoration of vertical bone height and new deposition of mineralized tissue in large calvarial bone defects after 8 weeks of miR-27 application. Implants containing PEG-PLGA-PLL-miR- 27 nanoparticles promoted matrix remodeling, new blood vessel formation, and substantial amounts of calvarial bone regeneration in critical size defects. On a cellular level, miR-27 overexpression increased alkaline phosphatase activity and bone marker gene expression, while inhibition of miR-27 resulted in a dramatic increase in the expression of osteoclastogenesis related genes and bone resorption. Both miR-24 and miR-27 promoted endothelial cell proliferation and blood vessel tube formation. Together, these exciting preliminary data prompted us to propose a novel molecular engineering strategy that will harness the osteogenic and pro-angiogenic qualities of miR-23/27/24 cluster members in conjunction with suitable scaffolds and re-balance alveolar and calvarial bone homeostasis for new craniofacial bone formation.
血管影响骨骼生理学的各个方面,包括矿物质生长 在新骨形成过程中。将骨骼改造成血管组织 专注于microRNA作为分子工程工具,因为它们能够 可逆地靶向多个调节网络。最近的研究从我们和其他 实验室已经证明,miRNA促进骨谱系分化, 通过WNT、BMP和Notch信号通路形成新骨, 骨吸收在我们寻求新的治疗方法,促进耦合骨 重塑和血管生成来治疗大面积骨缺损 发现miR-27~23~24 microRNA簇是一个非常有希望的候选miRNA 试剂.我们的初步分析揭示了多个miR-23和miR-27结合位点, Wnt拮抗剂Sfrp 1和Nlk 3 '的非翻译区(UTR), 与血管生成抑制剂BIM的UTR上的miR-24结合位点结合 和SEMA 4A证明了miR-27-23-24 microRNA簇对于 结合成骨和血管生成分子工程策略。 在初步研究中,我们已经证明miR-23-27-24簇成员 在炎性组织中表达大大降低。相反,miR-27模拟物 治疗具有严重垂直骨缺损的患病牙周组织, 80%完全恢复证明了意外广泛的新骨形成 垂直骨高度和新的矿化组织沉积在大颅骨 miR-27应用8周后的缺陷。含有PEG-PLGA-PLL-miR- 27纳米颗粒促进基质重塑,新血管形成, 在临界尺寸缺损中的大量颅骨再生。在细胞 水平,miR-27过表达增加碱性磷酸酶活性和骨标志物 基因表达,而抑制miR-27则导致细胞凋亡显著增加。 破骨细胞生成相关基因的表达与骨吸收。miR-24和 miR-27促进内皮细胞增殖和血管管形成。 总之,这些令人兴奋的初步数据促使我们提出了一种新的分子 工程策略,将利用成骨和促血管生成的质量, miR-23/27/24簇成员结合合适的支架和再平衡 牙槽骨和颅骨骨的动态平衡,以促进新的颅面骨形成。

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 }}

Xianghong Luan其他文献

Xianghong Luan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('Xianghong Luan', 18)}}的其他基金

New craniofacial bone engineering through miR-23-27-24 cluster mediated osteogenic angiogenic coupling
通过 miR-23-27-24 簇介导的成骨血管生成耦合的新颅面骨工程
  • 批准号:
    10935538
  • 财政年份:
    2023
  • 资助金额:
    $ 32.49万
  • 项目类别:
New craniofacial bone engineering through miR-23-27-24 cluster mediated osteogenic-angiogenic coupling
通过miR-23-27-24簇介导的成骨-血管生成耦合的新颅面骨工程
  • 批准号:
    10403608
  • 财政年份:
    2020
  • 资助金额:
    $ 32.49万
  • 项目类别:
New craniofacial bone engineering through miR-23-27-24 cluster mediated osteogenic-angiogenic coupling
通过miR-23-27-24簇介导的成骨-血管生成耦合的新颅面骨工程
  • 批准号:
    10619453
  • 财政年份:
    2020
  • 资助金额:
    $ 32.49万
  • 项目类别:
Small molecule microenvironment design for craniofacial bone regeneration
颅面骨再生的小分子微环境设计
  • 批准号:
    10190888
  • 财政年份:
    2009
  • 资助金额:
    $ 32.49万
  • 项目类别:
Epigenetics of Dental Stem Cells: Markers and CP27 Function
牙干细胞的表观遗传学:标记物和 CP27 功能
  • 批准号:
    7567145
  • 财政年份:
    2009
  • 资助金额:
    $ 32.49万
  • 项目类别:
Ameloblastin Function in Periodontal Development
成釉细胞在牙周发育中的功能
  • 批准号:
    7840797
  • 财政年份:
    2009
  • 资助金额:
    $ 32.49万
  • 项目类别:
Small molecule microenvironment design for craniofacial bone regeneration
颅面骨再生的小分子微环境设计
  • 批准号:
    10000905
  • 财政年份:
    2009
  • 资助金额:
    $ 32.49万
  • 项目类别:
Epigenetics of Dental Stem Cells: Markers and CP27 Function
牙干细胞的表观遗传学:标记物和 CP27 功能
  • 批准号:
    7896681
  • 财政年份:
    2009
  • 资助金额:
    $ 32.49万
  • 项目类别:
Enamel Structure Sophistication throuth Amelogenin Evolution
牙釉质结构通过牙釉蛋白进化而变得复杂
  • 批准号:
    8111783
  • 财政年份:
    2008
  • 资助金额:
    $ 32.49万
  • 项目类别:
Ameloblastin Function in Periodontal Development
成釉细胞在牙周发育中的功能
  • 批准号:
    8089487
  • 财政年份:
    2008
  • 资助金额:
    $ 32.49万
  • 项目类别:

相似海外基金

The role of tissue nonspecific alkaline phosphatase in brain endothelial cell homeostasis
组织非特异性碱性磷酸酶在脑内皮细胞稳态中的作用
  • 批准号:
    10220574
  • 财政年份:
    2021
  • 资助金额:
    $ 32.49万
  • 项目类别:
Post-Transcriptional Processing of the Small Intestinal Alkaline Phosphatase in the Postnatal Developing Pig
产后发育猪小肠碱性磷酸酶的转录后加工
  • 批准号:
    RGPIN-2016-05827
  • 财政年份:
    2021
  • 资助金额:
    $ 32.49万
  • 项目类别:
    Discovery Grants Program - Individual
The role of tissue nonspecific alkaline phosphatase in brain endothelial cell homeostasis
组织非特异性碱性磷酸酶在脑内皮细胞稳态中的作用
  • 批准号:
    10413987
  • 财政年份:
    2021
  • 资助金额:
    $ 32.49万
  • 项目类别:
The role of tissue nonspecific alkaline phosphatase in brain endothelial cell homeostasis
组织非特异性碱性磷酸酶在脑内皮细胞稳态中的作用
  • 批准号:
    10601067
  • 财政年份:
    2021
  • 资助金额:
    $ 32.49万
  • 项目类别:
Dietary induction of intestinal alkaline phosphatase intended to detoxify endotoxin and analysis of its mechanism of action.
膳食诱导肠道碱性磷酸酶解毒内毒素及其作用机制分析。
  • 批准号:
    20K05936
  • 财政年份:
    2020
  • 资助金额:
    $ 32.49万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Selective targeting of human alkaline phosphatase isozymes
选择性靶向人碱性磷酸酶同工酶
  • 批准号:
    10359823
  • 财政年份:
    2020
  • 资助金额:
    $ 32.49万
  • 项目类别:
Functional analysis of alkaline phosphatase, a stem cell marker, using human deciduous dental pulp cells derived from the patient with Hypophosphatasia (HPP)
使用源自低磷酸酯酶症 (HPP) 患者的人乳牙牙髓细胞对干细胞标记物碱性磷酸酶进行功能分析
  • 批准号:
    20K10210
  • 财政年份:
    2020
  • 资助金额:
    $ 32.49万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding the role of tissue non-specific alkaline phosphatase in osteogenesis for the therapy of hypophosphatasia.
了解组织非特异性碱性磷酸酶在成骨作用中的作用,以治疗低磷酸酯酶症。
  • 批准号:
    20K16894
  • 财政年份:
    2020
  • 资助金额:
    $ 32.49万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Selective targeting of human alkaline phosphatase isozymes
选择性靶向人碱性磷酸酶同工酶
  • 批准号:
    10117265
  • 财政年份:
    2020
  • 资助金额:
    $ 32.49万
  • 项目类别:
Post-Transcriptional Processing of the Small Intestinal Alkaline Phosphatase in the Postnatal Developing Pig
产后发育猪小肠碱性磷酸酶的转录后加工
  • 批准号:
    RGPIN-2016-05827
  • 财政年份:
    2020
  • 资助金额:
    $ 32.49万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了