作者
Megan M Weivoda, Ming Ruan, Christine M Hachfeld, Larry Pederson, Alan Howe, Rachel A Davey, Jeffrey D Zajac, Yasuhiro Kobayashi, Bart O Williams, Jennifer J Westendorf, Sundeep Khosla, Merry Jo Oursler
发表日期
2016/1/1
期刊
Journal of Bone and Mineral Research
卷号
31
期号
1
页码范围
65-75
出版商
John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
简介
Although there has been extensive characterization of the Wnt signaling pathway in the osteoblast lineage, the effects of Wnt proteins on the osteoclast lineage are less well studied. We found that osteoclast lineage cells express canonical Wnt receptors. Wnt3a reduced osteoclast formation when applied to early bone‐marrow macrophage (BMM) osteoclast differentiation cultures, whereas late addition did not suppress osteoclast formation. Early Wnt3a treatment inactivated the crucial transcription factor NFATc1 in osteoclast progenitors. Wnt3a led to the accumulation of nuclear β‐catenin, confirming activation of canonical Wnt signaling. Reducing low‐density lipoprotein receptor‐related proteins (Lrp) 5 and Lrp6 protein expression prevented Wnt3a‐induced inactivation of NFATc1; however, deletion of β‐catenin did not block Wnt3a inactivation of NFATc1, suggesting that this effect was mediated …
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