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PMID:14769860

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Citation

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 and Wagner, EF (2004) Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects. J. Cell Biol. 164:613-23

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.

Links

PubMed PMC2171977 Online version:10.1083/jcb.200308155

Keywords

Animals; Biological Markers; Bone Diseases, Metabolic/genetics; Bone Diseases, Metabolic/metabolism; Bone and Bones/cytology; Bone and Bones/metabolism; Bone and Bones/pathology; Cell Differentiation/physiology; Cell Division; Cell Lineage; Cells, Cultured; Female; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoblasts/cytology; Osteoblasts/physiology; Osteoclasts/cytology; Osteoclasts/physiology; Phenotype; Proto-Oncogene Proteins c-jun/genetics; Proto-Oncogene Proteins c-jun/metabolism; Tissue Distribution

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:JUNB

acts_upstream_of_or_within

GO:0030316: osteoclast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:JUNB

acts_upstream_of_or_within

GO:0001649: osteoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176174,MGI:MGI:3036209

P

Seeded From UniProt

complete

MOUSE:JUNB

acts_upstream_of_or_within

GO:0033687: osteoblast proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176174,MGI:MGI:3036209

P

Seeded From UniProt

complete


See also

References

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