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LRP8 mediates Wnt/β‐catenin signaling and controls osteoblast differentiation
Author(s) -
Zhang Juan,
Zhang Xiaofei,
Zhang Long,
Zhou Fangfang,
van Dinther Maarten,
ten Dijke Peter
Publication year - 2012
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.1661
Subject(s) - wnt signaling pathway , osteoblast , beta catenin , endocrinology , medicine , signal transduction , catenin , microbiology and biotechnology , biology , genetics , in vitro
The Wnt/β‐catenin signaling pathway plays a pivotal role in regulating osteoblast differentiation and bone formation. Here, we identify low‐density lipoprotein (LDL) receptor‐related protein 8 (LRP8) as a positive regulator of Wnt/β‐catenin signaling. In a small interfering RNA (siRNA) screen, LRP8 was shown to be required for Wnt/β‐catenin–induced transcriptional reporter activity. We found that ectopic expression of LRP8 increased Wnt‐induced transcriptional responses, and promoted Wnt‐induced β‐catenin accumulation. Moreover, knockdown of LRP8 resulted in a decrease in β‐catenin levels and suppression of Wnt/β‐catenin–induced Axin2 transcription. Functional studies in KS483 osteoprogenitor cells showed that LRP8 depletion resulted in impaired activation of endogenous Wnt‐induced genes and decreased osteoblast differentiation and mineralization, whereas LRP8 ectopic expression had the opposite effect. These results identify LRP8 as a novel positive factor of canonical Wnt signaling pathway and show its involvement in Wnt‐induced osteoblast differentiation. © 2012 American Society for Bone and Mineral Research.