Loss of β-catenin Induces Multifocal Periosteal Chondroma-Like Masses in Mice

Am J Pathol. 2013 Mar;182(3):917-27. doi: 10.1016/j.ajpath.2012.11.012. Epub 2012 Dec 25.

Abstract

Osteochondromas and enchondromas are the most common tumors affecting the skeleton. Osteochondromas can occur as multiple lesions, such as those in patients with hereditary multiple exostoses. Unexpectedly, while studying the role of β-catenin in cartilage development, we found that its conditional deletion induces ectopic chondroma-like cartilage formation in mice. Postnatal ablation of β-catenin in cartilage induced lateral outgrowth of the growth plate within 2 weeks after ablation. The chondroma-like masses were present in the flanking periosteum by 5 weeks and persisted for more than 6 months after β-catenin ablation. These long-lasting ectopic masses rarely contained apoptotic cells. In good correlation, transplants of β-catenin-deficient chondrocytes into athymic mice persisted for a longer period of time and resisted replacement by bone compared to control wild-type chondrocytes. In contrast, a β-catenin signaling stimulator increased cell death in control chondrocytes. Immunohistochemical analysis revealed that the amount of detectable β-catenin in cartilage cells of osteochondromas obtained from hereditary multiple exostoses patients was much lower than that in hypertrophic chondrocytes in normal human growth plates. The findings in our study indicate that loss of β-catenin expression in chondrocytes induces periosteal chondroma-like masses and may be linked to, and cause, the persistence of cartilage caps in osteochondromas.

Publication types

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

MeSH terms

  • Acid Phosphatase / metabolism
  • Animals
  • Apoptosis / drug effects
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cartilage / diagnostic imaging
  • Cartilage / pathology
  • Cell Proliferation / drug effects
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Chondrocytes / transplantation
  • Chondroma / diagnostic imaging
  • Chondroma / metabolism
  • Chondroma / pathology*
  • Choristoma / diagnostic imaging
  • Choristoma / pathology
  • Collagen Type II / metabolism
  • Growth Plate / drug effects
  • Growth Plate / metabolism
  • Growth Plate / pathology
  • Humans
  • In Situ Nick-End Labeling
  • Indoles / pharmacology
  • Integrases / metabolism
  • Isoenzymes / metabolism
  • Mice
  • Osteochondroma / metabolism
  • Osteochondroma / pathology
  • Oximes / pharmacology
  • Periosteum / diagnostic imaging
  • Periosteum / drug effects
  • Periosteum / metabolism
  • Periosteum / pathology*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Radiography
  • Ribs / pathology
  • Tamoxifen / pharmacology
  • Tartrate-Resistant Acid Phosphatase
  • beta Catenin / deficiency*
  • beta Catenin / metabolism

Substances

  • 6-bromoindirubin-3'-oxime
  • Collagen Type II
  • Indoles
  • Isoenzymes
  • Oximes
  • Proliferating Cell Nuclear Antigen
  • beta Catenin
  • Tamoxifen
  • Cre recombinase
  • Integrases
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase