Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-l

Bone formation by osteoblasts is essential for skeletal growth and remodeli ng. Fra-1 is a c-fos-related protein belonging to the AP-1 family of transc ription factors. Here we show that transgenic mice overexpressing Fra-1 in various organs develop a progressive increase in bone mass leading to osteo sclerosis of the entire skeleton, which is due to a cell-autonomous increas e in the number of mature osteoblasts. Moreover, osteoblast differentiation , but not proliferation, was enhanced and osteoclastogenesis was also eleva ted in vitro. These data indicate that, unlike c-Fos, which causes osteosar comas, Fra-1 specifically enhances bone formation, which may be exploited t o stimulate bone formation in pathological conditions.