Persistent expression of proto-oncogene c-fos stimulates osteoclast differentiation

We analyzed c-fos mRNA expression by northern blotting analysis in chicken osteoclast precursors which spontaneously differentiate to multinucleated osteoclasts in 5-6 days. Osteoclast precursors as well as mature multinucleated osteoclasts showed constitutive expression of c-fos mRNA which is not found in osteoblasts. The c-fos expression was enhanced transiently by serum, dibutyryl cAMP (10(-4) M) and phorbol 12-myristate 13-acetate (TPA) (5 x 10(-7) M). To clarify the role of c-fos in osteoclast differentiation, c-fos DNA was transfected into osteoclast precursors. Greater than 2 fold increases in tartrate resistant acid phosphatase (TRAP) and bone resorptive activity were observed in the transfected cells compared to controls 3 days after transfection, suggesting that prolonged expression of c-fos caused enhanced osteoclast differentiation.