R-spondin1 synergizes with Wnt3A in inducing osteoblast differentiation and osteoprotegerin expression

FEBS Lett. 2008 Mar 5;582(5):643-50. doi: 10.1016/j.febslet.2008.01.035. Epub 2008 Jan 31.

Abstract

R-spondins are a new group of Wnt/beta-catenin signaling agonists, however, the role of these proteins in bone remains unclear. We reported herein that R-sponin1 (Rspo1) acted synergistically with Wnt3A to activate Wnt/beta-catenin signaling in the uncommitted mesenchymal C2C12 cells. Furthermore, we found that Rspo1 at concentrations as low as 10 ng/ml synergized strongly with Wnt3A to induce C2C12 osteoblastic differentiation and osteoprotegerin expression. These events were blocked by Wnt/beta-catenin signaling antagonist Dickkopf-1. Finally, we demonstrated that Rspo1 synergized with Wnt3A to induce primary mouse osteoblast differentiation. Together, these findings suggest that Rpos1 may play an important role in bone remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Animals, Newborn
  • Cell Differentiation* / drug effects
  • Cell Line
  • Culture Media, Conditioned
  • Gene Expression Regulation / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • LDL-Receptor Related Proteins / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Mice
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Osteoblasts / enzymology
  • Osteoprotegerin / metabolism*
  • Phosphorylation / drug effects
  • Thermodynamics
  • Thrombospondins / genetics
  • Thrombospondins / metabolism*
  • Thrombospondins / pharmacology
  • Time Factors
  • Wnt Proteins / metabolism*
  • Wnt3 Protein
  • Wnt3A Protein
  • beta Catenin / metabolism

Substances

  • Culture Media, Conditioned
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • LDL-Receptor Related Proteins
  • LRP6 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Lrp6 protein, mouse
  • Osteoprotegerin
  • RSPO1 protein, human
  • RSPO1 protein, mouse
  • Thrombospondins
  • WNT3A protein, human
  • Wnt Proteins
  • Wnt3 Protein
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • beta Catenin
  • Alkaline Phosphatase