Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1.
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.
Jochum
W
W
Research Institute of Molecular Pathology (I.M.P.), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
David
J P
JP
Elliott
C
C
Wutz
A
A
Plenk
H
H
Matsuo
K
K
Wagner
E F
EF
D000818:Animals; D002114:Calcinosis / Q000235:genetics*; D002454:Cell Differentiation; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010026:Osteosclerosis / Q000235:genetics*; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics*; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D000099169:Fos-Related Antigen 1