Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects
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Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects. / Kenner, Lukas; Hoebertz, Astrid; Beil, F Timo; Beil, Timo; Keon, Niamh; Karreth, Florian; Eferl, Robert; Scheuch, Harald; Szremska, Agnieszka; Amling, Michael; Schorpp-Kistner, Marina; Angel, Peter; Wagner, Erwin F.
in: J CELL BIOL, Jahrgang 164, Nr. 4, 16.02.2004, S. 613-23.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects
AU - Kenner, Lukas
AU - Hoebertz, Astrid
AU - Beil, F Timo
AU - Beil, Timo
AU - Keon, Niamh
AU - Karreth, Florian
AU - Eferl, Robert
AU - Scheuch, Harald
AU - Szremska, Agnieszka
AU - Amling, Michael
AU - Schorpp-Kistner, Marina
AU - Angel, Peter
AU - Wagner, Erwin F
N1 - Copyright The Rockefeller University Press
PY - 2004/2/16
Y1 - 2004/2/16
N2 - Because JunB is an essential gene for placentation, it was conditionally deleted in the embryo proper. JunBDelta/Delta mice are born viable, but develop severe low turnover osteopenia caused by apparent cell-autonomous osteoblast and osteoclast defects before a chronic myeloid leukemia-like disease. Although JunB was reported to be a negative regulator of cell proliferation, junBDelta/Delta osteoclast precursors and osteoblasts show reduced proliferation along with a differentiation defect in vivo and in vitro. Mutant osteoblasts express elevated p16(INK4a) levels, but exhibit decreased cyclin D1 and cyclin A expression. Runx2 is transiently increased during osteoblast differentiation in vitro, whereas mature osteoblast markers such as osteocalcin and bone sialoprotein are strongly reduced. To support a cell-autonomous function of JunB in osteoclasts, junB was inactivated specifically in the macrophage-osteoclast lineage. Mutant mice develop an osteopetrosis-like phenotype with increased bone mass and reduced numbers of osteoclasts. Thus, these data reveal a novel function of JunB as a positive regulator controlling primarily osteoblast as well as osteoclast activity.
AB - Because JunB is an essential gene for placentation, it was conditionally deleted in the embryo proper. JunBDelta/Delta mice are born viable, but develop severe low turnover osteopenia caused by apparent cell-autonomous osteoblast and osteoclast defects before a chronic myeloid leukemia-like disease. Although JunB was reported to be a negative regulator of cell proliferation, junBDelta/Delta osteoclast precursors and osteoblasts show reduced proliferation along with a differentiation defect in vivo and in vitro. Mutant osteoblasts express elevated p16(INK4a) levels, but exhibit decreased cyclin D1 and cyclin A expression. Runx2 is transiently increased during osteoblast differentiation in vitro, whereas mature osteoblast markers such as osteocalcin and bone sialoprotein are strongly reduced. To support a cell-autonomous function of JunB in osteoclasts, junB was inactivated specifically in the macrophage-osteoclast lineage. Mutant mice develop an osteopetrosis-like phenotype with increased bone mass and reduced numbers of osteoclasts. Thus, these data reveal a novel function of JunB as a positive regulator controlling primarily osteoblast as well as osteoclast activity.
KW - Animals
KW - Biological Markers
KW - Bone Diseases, Metabolic
KW - Bone and Bones
KW - Cell Differentiation
KW - Cell Division
KW - Cell Lineage
KW - Cells, Cultured
KW - Female
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Osteoblasts
KW - Osteoclasts
KW - Phenotype
KW - Proto-Oncogene Proteins c-jun
KW - Tissue Distribution
U2 - 10.1083/jcb.200308155
DO - 10.1083/jcb.200308155
M3 - SCORING: Journal article
C2 - 14769860
VL - 164
SP - 613
EP - 623
JO - J CELL BIOL
JF - J CELL BIOL
SN - 0021-9525
IS - 4
ER -