Bone regeneration is regulated by Wnt signaling
Bone regeneration is regulated by Wnt signaling
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DOI：
10.1359/jbmr.070802
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发表时间：
2007-12-01
影响因子：
6.2
通讯作者：
Helms, Jill A.
中科院分区：
文献类型：
--
作者：
Kim, Jae-Beorn;Leucht, Philipp;Helms, Jill A.
越来越多的人认为，组织再生是一种发育过程的重新激活，如果使用不当，可能会导致恶性生长。因此，了解支配组织再生的分子和细胞途径有助于了解正常发育以及对癌症等病理情况的洞察。在此，我们研究了Wnt信号在骨组织再生中的作用。前言：一些成人组织具有再生能力，骨是其中最引人注目的组织之一。骨骼在损伤后表现出持续的、终生的改造能力，而持续的骨再生是保持骨量和密度的先决条件。即使是骨骼再生的轻微干扰也会产生深远的后果，例如骨质疏松和骨骼修复延迟等情况。在这里，我们的目标是确定WNT在成人骨再生中的作用。材料和方法：利用TOPga报告小鼠，我们发现骨骼损伤激发了WNT报告活性，特别是在损伤部位。我们使用骨骼损伤模型显示，通过在成人骨骼中腺病毒表达Dkk1而实现的Wnt抑制可以阻止骨祖细胞的分化。结果：与对照组相比，损伤诱导的骨再生减少了84%。LRP5 Wnt共受体突变导致Wnt途径的结构性激活导致骨量增加，但我们的实验表明，这个相同的点突变导致骨再生延迟。在这些转基因小鼠中，损伤部位的骨祖细胞保持在增殖状态，向成骨细胞的分化被推迟。结论：综合考虑，这些数据为理解Wnt信号在成人骨再生中的作用提供了一个框架，并为治疗需要增强骨形成的临床疾病提供了一种可行的方法。
Tissue regeneration is increasingly viewed as reactivation of a developmental process that, when misappropriated, can lead to malignant growth. Therefore, understanding the molecular and cellular pathways that govern tissue regeneration provides a glimpse into normal development as well as insights into pathological conditions such as cancer. Herein, we studied the role of Wnt signaling in skeletal tissue regeneration.Introduction: Some adult tissues have the ability to regenerate, and among these, bone is one of the most remarkable. Bone exhibits a persistent, lifelong capacity to reform after injury, and continual bone regeneration is a prerequisite to maintaining bone mass and density. Even slight perturbations in bone regeneration can have profound consequences, as exemplified by conditions such as osteoporosis and delayed skeletal repair. Here, our goal was to determine the role of Wnts in adult bone regeneration.Materials and Methods: Using TOPgal reporter mice, we found that damage to the skeleton instigated Wnt reporter activity, specifically at the site of injury. We used a skeletal injury model to show that Wnt inhibition, achieved through adenoviral expression of Dkk1 in the adult skeleton, prevented the differentiation of osteoprogenitor cells.Results: As a result, injury-induced bone regeneration was reduced by 84% compared with controls. Constitutive activation of the Wnt pathway resulting from a mutation in the Lrp5 Wnt co-receptor results in high bone mass, but our experiments showed that this same point mutation caused a delay in bone regeneration. In these transgenic mice, osteoprogenitor cells in the injury site were maintained in a proliferative state and differentiation into osteoblasts was delayed.Conclusions: When considered together, these data provide a framework for understanding the roles of Wnt signaling in adult bone regeneration and suggest a feasible approach to treating clinical conditions where enhanced bone formation is desired.