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PMID: 14769860 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects.

The Journal of cell biology ·Vol. 164 ·No. 4 ·2004-02-16 ·Pages 613-23

Kenner L, Hoebertz A, Beil FT, Beil T, Keon N, Karreth F, Eferl R, Scheuch H, Szremska A, Amling M, Schorpp-Kistner M, Angel P, Wagner EF

Abstract

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.

MeSH Terms
Animals Biomarkers Bone Diseases, Metabolic/genetics,metabolism Bone and Bones/cytology,metabolism,pathology Cell Differentiation/physiology Cell Division Cell Lineage Cells, Cultured Female Mice Mice, Inbred C57BL Mice, Knockout Osteoblasts/cytology,physiology Osteoclasts/cytology,physiology Phenotype Proto-Oncogene Proteins c-jun/genetics,metabolism Tissue Distribution
Chemicals
Biomarkers Proto-Oncogene Proteins c-jun
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Kenner Lukas
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
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
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200308155
Published
2004-02-16
Epub
2004-00-09
Pages
613-23
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171977
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1083/jcb.200308155 PMC Full Text View journal details
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