Parathyroid hormone signaling through low-density lipoprotein-related protein 6

Mei Wan, Chaozhe Yang, Jun Li, Xiangwei Wu, Hongling Yuan, Hairong Ma, Xi He, Shuyi Nie, Chenbei Chang, Xu Cao

Research output: Contribution to journalArticlepeer-review

Abstract

Intermittent administration of PTH stimulates bone formation, but the precise mechanisms responsible for PTH responses in osteoblasts are only incompletely understood. Here we show that binding of PTH to its receptor PTH1R induced association of LRP6, a coreceptor of Wnt, with PTH1R. The formation of the ternary complex containing PTH, PTH1R, and LRP6 promoted rapid phosphorylation of LRP6, which resulted in the recruitment of axin to LRP6, and stabilization of β-catenin. Activation of PKA is essential for PTH-induced β-catenin stabilization, but not for Wnt signaling. In vivo studies confirmed that PTH treatment led to phosphorylation of LRP6 and an increase in amount of β-catenin in osteoblasts with a concurrent increase in bone formation in rat. Thus, LRP6 coreceptor is a key element of the PTH signaling that regulates osteoblast activity.

Original languageEnglish (US)
Pages (from-to)2968-2979
Number of pages12
JournalGenes and Development
Volume22
Issue number21
DOIs
StatePublished - Nov 1 2008

Keywords

  • LRP6
  • Osteoblasts
  • PKA
  • PTH signaling
  • β-catenin

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'Parathyroid hormone signaling through low-density lipoprotein-related protein 6'. Together they form a unique fingerprint.

Cite this