Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production.
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Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production. / Bozec, Aline; Bakiri, Latifa; Jimenez, Maria; Schinke, Thorsten; Amling, Michael; Wagner, Erwin F.
in: J CELL BIOL, Jahrgang 190, Nr. 6, 6, 2010, S. 1093-1106.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production.
AU - Bozec, Aline
AU - Bakiri, Latifa
AU - Jimenez, Maria
AU - Schinke, Thorsten
AU - Amling, Michael
AU - Wagner, Erwin F
PY - 2010
Y1 - 2010
N2 - The activator protein-1 (AP-1) transcription factor complex, in particular the Fos proteins, is an important regulator of bone homeostasis. Fra-2 (Fosl2), a Fos-related protein of the AP-1 family, is expressed in bone cells, and newborn mice lacking Fra-2 exhibit defects in chondrocytes and osteoclasts. Here we show that Fra-2-deficient osteoblasts display a differentiation defect both in vivo and in vitro. Moreover, Fra-2-overexpressing mice are osteosclerotic because of increased differentiation of osteoblasts, which appears to be cell autonomous. Importantly, the osteoblast-specific osteocalcin (Oc) gene and collagen1 2 (col1 2) are transcriptional targets of Fra-2 in both murine and human bone cells. In addition, Fra-2, Oc, and col1 are expressed in stromal cells of human chondroblastic and osteoblastic osteosarcomas (Os's) as well as during osteoblast differentiation of human Os cell lines. These findings reveal a novel function of Fra-2/AP-1 as a positive regulator of bone and matrix formation in mice and humans.
AB - The activator protein-1 (AP-1) transcription factor complex, in particular the Fos proteins, is an important regulator of bone homeostasis. Fra-2 (Fosl2), a Fos-related protein of the AP-1 family, is expressed in bone cells, and newborn mice lacking Fra-2 exhibit defects in chondrocytes and osteoclasts. Here we show that Fra-2-deficient osteoblasts display a differentiation defect both in vivo and in vitro. Moreover, Fra-2-overexpressing mice are osteosclerotic because of increased differentiation of osteoblasts, which appears to be cell autonomous. Importantly, the osteoblast-specific osteocalcin (Oc) gene and collagen1 2 (col1 2) are transcriptional targets of Fra-2 in both murine and human bone cells. In addition, Fra-2, Oc, and col1 are expressed in stromal cells of human chondroblastic and osteoblastic osteosarcomas (Os's) as well as during osteoblast differentiation of human Os cell lines. These findings reveal a novel function of Fra-2/AP-1 as a positive regulator of bone and matrix formation in mice and humans.
M3 - SCORING: Zeitschriftenaufsatz
VL - 190
SP - 1093
EP - 1106
JO - J CELL BIOL
JF - J CELL BIOL
SN - 0021-9525
IS - 6
M1 - 6
ER -