Role of FGF9 and FGF receptor 3 in osteochondroma formation.

Osteochondromas are chondro-osseous protuberances that occur in metaphyses of long bones. The cartilaginous cap is assumed to be responsible for the growth of the lesions during childhood and adolescence, but mitotic figures are rarely seen in the cap. Therefore, another cell population, probably mesenchymal cells, is responsible for proliferation and growth. Residual mesenchymal cells capable of rapid proliferation are difficult to detect due to lack of specific histologic features. Two specific markers for mesenchymal cells, FGF receptor 3 (FGFR3) and collagen type IIa, have been described. Osteochondroma mesenchymal cells are found in the soft tissues overlying the cartilage cap. The surrounding areas of typical cartilage are negative for both mesenchymal cell associated antigens. The soft tissues overlying the cartilage do not have cartilaginous features. The undifferentiated cells overlying the exostosis yield in culture a rapidly proliferating homogenous population of fibroblast-like cells. Expression at the mRNA level of FGF9, FGFR3, and collagen type IIa is found in these cells, but not in skin fibroblasts from afflicted or healthy individuals. Exogenous administration of TGFbeta1 to cultures of hereditary multiple exostosis eliminates FGF9 expression. These results indicate fibrous regions contain the mesenchymal cells responsible for osteochondroma growth.