Bone regeneration is regulated by wnt signaling

JOURNAL OF BONE AND MINERAL RESEARCH
Volume 22, Number 12, 2007
Published online on August 13, 2007; doi: 10.1359/JBMR.070802
© 2007 American Society for Bone and Mineral Research

Bone Regeneration Is Regulated by Wnt Signaling
Jae-Beom Kim,1,2 Philipp Leucht,1,2,3 Kentson Lam,1 Cynthia Luppen,1 Derk Ten Berge,4 Roel Nusse,4 and
Jill A Helms1

ABSTRACT: 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,