[The pathogenesis and etiology of giant cell tumor of bone from a viewpoint of bone resorptive factors].
The pathogenesis and etiology of giant cell tumor of bone was studied by analysing the bone resorptive factors in the conditioned culture medium. In the primary culture characteristic multinucleated giant cells and mononuclear cells were coexisted. The values of interleukin 1 (IL-1) and prostaglandin E2 (PGE2) in the conditioned medium obtained from the primary culture were high. In the primary culture, an immunohistochemical technique revealed the presence of IL-1 both in mononuclear cells and in giant cells. When the medium obtained from the primary culture was tested for proteolytic activity by zymography with SDS/polyacrylamide containing gelatin, multiple gelatinolytic activities were observed. In subcultures, multinucleated giant cells were not persisted and only stromal cells were visible. In subcultures, the values of IL-1 and PGE2 were much lower. Proteolytic activities were similarly weak. However, the exposure of the passaged stromal cells to the medium containing IL-1 stimulated the stromal cells to produce PGE2 and proteolytic enzymes. Immunofluorescent localization technique revealed the expression of the proteolytic enzymes in the stromal cells. These findings demonstrated that coexistence of multinucleated giant cells with mononuclear cells should be needed for the tumor to express the original phenotype. In the presence of multi-nucleated cells, mononuclear cells seem to be stimulated to produce PGE2 and proteolytic enzymes, which accelerate the bone resorption. These factors are considered to act synergetically in the resorption of bones.