Article

In Vivo Analysis of Wnt Signaling in Bone

Department of Genetics and Development, Columbia University, New York, New York, United States
Endocrinology (Impact Factor: 4.5). 06/2007; 148(6):2630-4. DOI: 10.1210/en.2006-1372
Source: PubMed

ABSTRACT

Bone remodeling requires osteoblasts and osteoclasts working in concert to maintain a constant bone mass. The dysregulation of signaling pathways that affect osteoblast or osteoclast differentiation or function leads to either osteopenia or high bone mass. The discovery that activating and inactivating mutations in low-density lipoprotein receptor-related protein 5, a putative Wnt coreceptor, led to high bone mass and low bone mass in human beings, respectively, generated a tremendous amount of interest in the possible role of the Wnt signaling pathway in the regulation of bone remodeling. A number of mouse models have been generated to study a collection of Wnt signaling molecules that have been identified as regulators of bone mass. These mouse models help establish the canonical Wnt signaling pathway as a major regulator of chondrogenesis, osteoblastogenesis, and osteoclastogenesis. This review will summarize these advances.

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    • "During new bone layer formation, osteoblasts differentiate into terminal stage osteocytes. The canonical Wnt signaling pathway plays a crucial role in normal bone development[21,858687888990919293949596in the regulation of both osteoblasts and osteoclasts (Figure 2). In osteoblasts, Wnt signaling influences three major developmental functions: the commitment of MSCs to an osteoblast stem cell type; stimulation of osteoblast proliferation; and promotion of osteoblast and osteocyte survival[ "

    Full-text · Dataset · Jan 2016
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    • "Bone anabolic stimuli activate this pathway and human mutations of components along this pathway underscore its crucial role in bone accrual and maintenance. However, the cell responsible for orchestrating Wnt anabolic actions has remained elusive, as activation of Wnt/β-catenin signaling in preosteoblasts or osteoblasts inhibits resorption without increasing bone forma- tion[33]. This new evidence now showed that, in contrast, activation of canonical Wnt signaling in osteocytes [dominant active (da)βcat Ot mice] induces bone anabolism and triggers Notch signaling without affecting survival[32•]. "
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