课题基金 / 基金详情

项目摘要

项目成果

Mimi C Sammarco的其他基金

相似基金

相关文献

中文摘要
翻译
肢体损伤后的再生是一个复杂且耗费精力的过程。在这个过程中,祖先 增殖、成骨细胞分化和矿物质沉积都需要足够的生物建筑供应。 盖帽和ATP(1-5)。然而,细胞代谢的贡献及其对骨骼再生的遗传控制 在很大程度上是未知的,这代表着一个重大的知识差距。使用已建立的小鼠指尖截肢 模型中,我们发现小鼠在衰老过程中表现出再生能力受损,并且这种损伤与 与幼鼠相比,糖酵解和氧化磷酸化(OxPhos)基因的表达增加。 这些令人兴奋的初步结果引导我们研究了代谢和遗传机制。 骨骼再生。 我们的初步发现支持骨骼再生是依赖新陈代谢的,可以通过 外源代谢物和基因表达。这些数据表明, 草酰乙酸酯(OAA)是一种促进糖酵解和促进呼吸的代谢物,可增加再生骨体积和 鼠标模型中的厚度。或者,含有1(Ctrc1)的胶原蛋白三螺旋重复序列的调制还 改变骨骼再生。Ctrc1在胚泡中特异表达,即去分化的组织结构。 再生的中枢,Ctrc1-/-小鼠表现出再生受损和细胞失调 新陈代谢。此外,我们的初步数据显示,OAA治疗增加了Ctrc1的表达, 加强新陈代谢和基因控制之间的直接联系。我们假设一种微调的相互作用 细胞新陈代谢和遗传控制之间协同调节细胞功能,这种相互作用可以 在外源(OAA)和基因水平(Ctrc1)上都受到操纵,以调节再生结果。
英文摘要
Limb regeneration after injury is a sophisticated and energetically expensive process. In this process, progenitor proliferation, osteoblast differentiation and mineral deposition all require sufficient supplies of biological building blocks and ATP(1-5). However, the contribution of cell metabolism and its genetic control of skeletal regeneration is largely unknown, representing a major knowledge gap. Using the established mouse digit tip amputation model, we found that mice exhibit impaired regeneration during aging, and that this impairment is linked to increased expression of glycolysis and oxidative phosphorylation (OxPhos) genes, compared to young mice. These exciting preliminary results have led us to investigate the metabolic and genetic mechanisms that underlie skeletal regeneration. Our preliminary findings support that skeletal regeneration is metabolism-dependent and can be manipulated by exogenous metabolites and gene expression, respectively. These data suggest that administration of oxaloacetate (OAA), a pro-glycolytic and pro-respiratory metabolite, increases regenerated bone volume and thickness in a mouse model. Alternatively, modulation of collagen triple helix repeat containing 1 (Cthrc1) also alters skeletal regeneration. Cthrc1 is specifically expressed in the blastema, the dedifferentiated tissue structure central to regeneration, and Cthrc1-/- mice demonstrated impaired regeneration and dysregulated cell metabolism. Moreover, our preliminary data show that treatment with OAA increases Cthrc1 expression, reinforcing a direct link between metabolism and genetic control. We hypothesize that a finely tuned interaction between cell metabolism and genetic control synergistically regulates cell function, and that this interaction can be manipulated both exogenously (OAA) and at a gene level (Cthrc1) to modulate regenerative outcomes.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Cellular metabolism at the crossroads of skeletal regeneration
  • 批准号:
    10529832
  • 项目类别:
  • 资助金额:
    $35.09万
  • 财政年份:
    2022
  • 负责人:
    Mimi C Sammarco
  • 依托单位:
Genomics, Bioinformatics, and Molecular Imaging Core
  • 批准号:
    10631206
  • 项目类别:
  • 资助金额:
    $54.49万
  • 财政年份:
    2022
  • 负责人:
    Mimi C Sammarco
  • 依托单位:
Spatiotemporal regulation of digit regeneration by sensory nerves
  • 批准号:
    10452887
  • 项目类别:
  • 资助金额:
    $24.43万
  • 财政年份:
    2022
  • 负责人:
    Mimi C Sammarco
  • 依托单位:
Spatiotemporal regulation of digit regeneration by sensory nerves
  • 批准号:
    10599298
  • 项目类别:
  • 资助金额:
    $11.5万
  • 财政年份:
    2022
  • 负责人:
    Mimi C Sammarco
  • 依托单位:
海外基金