Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects.
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.
Kenner
Lukas
L
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Hoebertz
Astrid
A
Beil
F Timo
FT
Beil
Timo
T
Keon
Niamh
N
Karreth
Florian
F
Eferl
Robert
R
Scheuch
Harald
H
Szremska
Agnieszka
A
Amling
Michael
M
Schorpp-Kistner
Marina
M
Angel
Peter
P
Wagner
Erwin F
EF
D000818:Animals; D015415:Biomarkers; D001851:Bone Diseases, Metabolic / Q000235:genetics / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D015415:Biomarkers; D016755:Proto-Oncogene Proteins c-jun