Characterization of Wnt/beta-catenin signalling in osteoclasts in multiple myeloma

Br J Haematol. 2010 Mar;148(5):726-38. doi: 10.1111/j.1365-2141.2009.08009.x. Epub 2009 Nov 24.


We recently showed that increasing Wnt/beta-catenin signalling in the bone marrow microenvironment or in multiple myeloma (MM) cells clearly suppresses osteoclastogenesis in SCID-hu mice; however, this regulation of osteoclastogenesis could result directly from activation of Wnt/beta-catenin signalling in osteoclasts or indirectly from effects on osteoblasts. The present studies characterized Wnt/beta-catenin signalling and its potential role in osteoclasts. Systematic analysis of expression of WNT, FZD, LRP and TCF gene families demonstrated that numerous Wnt-signalling components were expressed in human osteoclasts from patients with MM. Functional Wnt/beta-catenin signalling was identified by accumulation of total and active beta-catenin and increases in Dvl-3 protein in response to Wnt3a or LiCl. Furthermore, Wnt-induced increases in beta-catenin and Dvl-3 were attenuated by Wnt antagonists Dkk1 and sFRP1. Finally, Wnt3a-induced TCF/LEF transcriptional activity suggests that canonical Wnt signalling is active in osteoclasts. Supernatants from dominant-negative-beta-catenin-expressing osteoblast clones significantly stimulated tartrate-resistant acid phosphatase-positive osteoclast formation from primary MM-derived osteoclasts, compared with supernatants from control cells. These results suggested that Wnt/beta-catenin signalling is active in osteoclasts in MM and is involved in osteoclastogenesis in bone marrow, where it acts as a negative regulator of osteoclast formation in an osteoblast-dependent manner in MM.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Line, Tumor
  • Dishevelled Proteins
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism
  • Genes, Reporter / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Luciferases / metabolism
  • Mice
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism*
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism*
  • Osteogenesis / physiology
  • Phosphoproteins / metabolism
  • Signal Transduction / physiology
  • Wnt Proteins / antagonists & inhibitors
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • Adaptor Proteins, Signal Transducing
  • DVL3 protein, human
  • Dishevelled Proteins
  • Dvl3 protein, mouse
  • FZD1 protein, human
  • Frizzled Receptors
  • Intercellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Wnt Proteins
  • beta Catenin
  • Luciferases