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

被引:246
作者
Jochum, W
David, JP
Elliott, C
Wutz, A
Plenk, H
Matsuo, K
Wagner, EF
机构
[1] Res Inst Mol Pathol, A-1030 Vienna, Austria
[2] Univ Vienna, Inst Histol & Embryol Bone & Biomat Res, A-1090 Vienna, Austria
基金
奥地利科学基金会;
关键词
D O I
10.1038/79676
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:980 / 984
页数:5
相关论文
共 31 条
  • [1] THE ROLE OF JUN, FOS AND THE AP-1 COMPLEX IN CELL-PROLIFERATION AND TRANSFORMATION
    ANGEL, P
    KARIN, M
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (2-3) : 129 - 157
  • [2] CHAMBERS TJ, 2000, IN PRESS J PATHOL
  • [3] FRA-1 - A SERUM-INDUCIBLE, CELLULAR IMMEDIATE-EARLY GENE THAT ENCODES A FOS-RELATED ANTIGEN
    COHEN, DR
    CURRAN, T
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1988, 8 (05) : 2063 - 2069
  • [4] THE PRODUCT OF A FOS-RELATED GENE, FRA-1, BINDS COOPERATIVELY TO THE AP-1 SITE WITH JUN - TRANSCRIPTION FACTOR AP-1 IS COMPRISED OF MULTIPLE PROTEIN COMPLEXES
    COHEN, DR
    FERREIRA, PCP
    GENTZ, R
    FRANZA, BR
    CURRAN, T
    [J]. GENES & DEVELOPMENT, 1989, 3 (02) : 173 - 184
  • [5] Increased bone formation in osteocalcin-deficient mice
    Ducy, P
    Desbois, C
    Boyce, B
    Pinero, G
    Story, B
    Dunstan, C
    Smith, E
    Bonadio, J
    Goldstein, S
    Gundberg, C
    Bradley, A
    Karsenty, G
    [J]. NATURE, 1996, 382 (6590) : 448 - 452
  • [6] Leptin inhibits bone formation through a hypothalamic relay: A central control of bone mass
    Ducy, P
    Amling, M
    Takeda, S
    Priemel, M
    Schilling, AF
    Beil, FT
    Shen, JH
    Vinson, C
    Rueger, JM
    Karsenty, G
    [J]. CELL, 2000, 100 (02) : 197 - 207
  • [7] A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development
    Ducy, P
    Starbuck, M
    Priemel, M
    Shen, JH
    Pinero, G
    Geoffroy, V
    Amling, M
    Karsenty, G
    [J]. GENES & DEVELOPMENT, 1999, 13 (08) : 1025 - 1036
  • [8] TOWARD A MOLECULAR UNDERSTANDING OF SKELETAL DEVELOPMENT
    ERLEBACHER, A
    FILVAROFF, EH
    GITELMAN, SE
    DERYNCK, R
    [J]. CELL, 1995, 80 (03) : 371 - 378
  • [9] Bone remodelling: A signalling system for osteoclast regulation
    Filvaroff, E
    Derynck, R
    [J]. CURRENT BIOLOGY, 1998, 8 (19) : R679 - R682
  • [10] FOS AND BONE CELL-DEVELOPMENT - LESSONS FROM A NUCLEAR ONCOGENE
    GRIGORIADIS, AE
    WANG, ZQ
    WAGNER, EF
    [J]. TRENDS IN GENETICS, 1995, 11 (11) : 436 - 441