Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1

W Jochum, JP David, C Elliott, A Wutz, H Plenk… - Nature medicine, 2000 - nature.com
W Jochum, JP David, C Elliott, A Wutz, H Plenk, K Matsuo, EF Wagner
Nature medicine, 2000nature.com
Bone formation by osteoblasts is essential for skeletal growth and remodeling. Fra-1 is a c-
Fos-related protein belonging to the AP-1 family of transcription factors. Here we show that
transgenic mice overexpressing Fra-1 in various organs develop a progressive increase in
bone mass leading to osteosclerosis of the entire skeleton, which is due to a cell-
autonomous increase in the number of mature osteoblasts. Moreover, osteoblast
differentiation, but not proliferation, was enhanced and osteoclastogenesis was also …
Abstract
Bone formation by osteoblasts is essential for skeletal growth and remodeling. Fra-1 is a c-Fos-related protein belonging to the AP-1 family of transcription factors. Here we show that transgenic mice overexpressing Fra-1 in various organs develop a progressive increase in bone mass leading to osteosclerosis of the entire skeleton, which is due to a cell-autonomous increase in the number of mature osteoblasts. Moreover, osteoblast differentiation, but not proliferation, was enhanced and osteoclastogenesis was also elevated in vitro. These data indicate that, unlike c-Fos, which causes osteosarcomas, Fra-1 specifically enhances bone formation, which may be exploited to stimulate bone formation in pathological conditions.
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