PP60(C-SRC) EXPRESSION IN OSTEOCLASTS FROM OSTEOPETROTIC CHILDREN ANDIN GIANT TUMOR-CELLS

Malignant infantile osteopetrosis is a severe congenital disease chara cterized by impaired osteoclast activity. Among the multiple factors t hat influence bone resorption, the c-src protoncogene product pp60(c-s rc) plays an essential role, since mice which lack pp60(c-src) develop osteopetrosis. To gain insight into the possible role of pp60(c-csrc) in the pathogenesis of infantile osteopetrosis, we examined the osteo clasts of three children displaying the typical features of the diseas e, aged respectively one, four and seven months. pp60(c-csrc) expressi on and localization, together with the expression of a 80/85-kilodalto n pp60(c-src) substrate, cortactin, were examined by immunoelectron mi croscopy. Osteoclasts from two giant cell tumors were used as controls . Bone and tumor samples were fixed in 4% paraformaldehyde, included i n LR-White resin at -30 degrees C and the sections processed with mAb 327 or mAb anti p80/85 by an immunogold technique. pp60(c-src) was exp ressed in the cytoplasm, in nuclear membranes and in nuclei of the ost eoclasts of the three osteopetrotic children. The subcellular localiza tion of the kinase was not different from the localization in giant tu mor cells. In both cases cortactin was abundant. In conclusion, in thr ee children with malignant osteopetrosis, pp60(c-src) expression in os teoclasts does not appear to be involved in the pathogenesis of the di sease. The presence of this protein, however, does not necessarily ref lect normal c-src tyrosine kinase activity, nor normal c-src-dependent intracellular signaling pathways. Moreover the presence of the protei n in nuclear membranes, and especially around nuclear pores supports t he hypothesis that in osteoclasts, c-src may participate in the regula tion of RNA processing.