期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：49
页码：E5262-E5271
DOI：10.1073/pnas.1420463111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceDespite the importance of Wnt signaling in bone biology, there is a knowledge gap in the identity of the cells that produce the Wnt ligands and the functions of Wnts produced by specific cell types. In our study, we comprehensively characterized the expression patterns of all 19 Wnts in the developing mouse bone by in situ hybridization, and further showed that Osterix-expressing cells can produce Wnts and respond to Wnt signaling. Additionally, we found that Wnts produced by these Osterix-expressing cells regulate their differentiation and proliferation. Through providing a better understanding of how Wnt signaling contributes to bone biology, our findings also have clinical implications for the mechanism of the osteoporotic drug that targets Sclerostin, a Wnt signaling antagonist. 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.
