UP-REGULATION OF C-FOS PROTOONCOGENE EXPRESSION IN PAGETIC OSTEOCLASTS

Using in situ hybridization we show that expression of the c-fos oncog ene, a gene normally associated with osteosarcomas, is greatly elevate d in osteoclasts of patients with Paget's disease. Immunohistochemical staining with c-fos antibodies also shows increased protein in pageti c osteoclasts. In light of transgenic mouse experiments showing a key role for c-fos in bone resorption, we propose that elevated c-fos gene expression in pagetic osteoclasts is an important component in produc ing the pagetic phenotype. Levels of c-fos gene and protein expression in pagetic osteoblasts are lower than those detected in osteoclasts b ut still higher than in nonpagetic osteoblasts. This may provide an ex planation for the increased incidence of osteosarcomas in patients wit h Paget's disease because overexpression of c-fos in osteoblasts of tr ansgenic mice induces osteosarcoma formation.