TOPGAL Mice Show That the Canonical Wnt Signaling Pathway Is Active During Bone Development and Growth and Is Activated by Mechanical Loading In Vitro

• DOI: 10.1359/jbmr.050210
• Publication Date: 2006-04-27T08:53:54Z
• Authors: Julie R Hens; Kimberly M Wilson; Pamela Dann; Xuesong Chen; Mark C Horowitz; John J Wysolmerski
• Keywords: LRP5; LRP6; Beta-catenin; WNT3A

Abstract We identified cellular targets of canonical Wnt signaling within the skeleton, which included chondrocytes, osteoblasts, and osteocytes in growing bone, but only chondrocytes mature skeleton. Mechanical deformation induced osteoblasts vitro. Introduction: Genetic evidence mice humans has implicated pathway control skeletal development bone mass. However, little is known details skeleton vivo. used indicator TOPGAL to identify cells activated this during Materials Methods: examined embryonic neonatal mice. The transgene consists a β-galactosidase gene driven by T cell factor (TCF)β-catenin responsive promoter so that activity can be detected X-gal staining. Expression components was primary calvarial cultures RT-PCR. effect mechanical on grown collagen I stretched using Flexercell Tension Plus System FX-4000T. Immunohistochemistry examine localization β-catenin cartilage, cultured exposed physical deformation. Results Conclusions: Canonical active several types fetal including osteocytes. With age, activation became less prominent persisted Although culture expressed many different individual Wnt's receptors, not these at baseline. Together with seen vivo, data suggest may involved coupling force anabolic