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

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 beta-catenin in cartilage development, we found that its conditional deletion induces ectopic chondroma-like cartilage formation in mice. Postnatal ablation of beta-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 beta-catenin ablation. These long-lasting ectopic masses rarely contained apoptotic cells. In good correlation, transplants of beta-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 beta-catenin signaling stimulator increased cell death in control chondrocytes. Immunohistochemical analysis revealed that the amount of detectable beta-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 beta-catenin expression in chondrocytes induces periosteal chondroma-like masses and may be linked to, and cause, the persistence of cartilage caps in osteochondromas. (Am J Pathol 2013, 182: 917-927; http://dx.doi.org/10.1016/j.ajpath.2012.11.012)