Wnts Produced by Osterix-expressing Osteolineage Cells Regulate Their Proliferation and Differentiation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2014 Nov 26

PMID 25422448

Citations 33

Authors

Si Hui Tan

Kshemendra Senarath-Yapa

Michael T Chung

Michael T Longaker

Joy Y Wu

Roeland Nusse

Affiliations

Soon will be listed here.

Abstract

Wnt signaling is a critical regulator of bone development, but the identity and role of the Wnt-producing cells are still unclear. We addressed these questions through in situ hybridization, lineage tracing, and genetic experiments. First, we surveyed the expression of all 19 Wnt genes and Wnt target gene Axin2 in the neonatal mouse bone by in situ hybridization, and demonstrated--to our knowledge for the first time--that Osterix-expressing cells coexpress Wnt and Axin2. To track the behavior and cell fate of Axin2-expressing osteolineage cells, we performed lineage tracing and showed that they sustain bone formation over the long term. Finally, to examine the role of Wnts produced by Osterix-expressing cells, we inhibited Wnt secretion in vivo, and observed inappropriate differentiation, impaired proliferation, and diminished Wnt signaling response. Therefore, Osterix-expressing cells produce their own Wnts that in turn induce Wnt signaling response, thereby regulating their proliferation and differentiation.

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