Because JunB is an essential gene for placentation, it was conditionally deleted in the embryo proper. JunBΔ/Δ 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, junBΔ/Δ osteoclast precursors and osteoblasts show reduced proliferation along with a differentiation defect in vivo and in vitro. Mutant osteoblasts express elevated p16INK4a 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.
Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects
L. Kenner and A. Hoebertz contributed equally to this paper.
Abbreviations used in this paper: AP-1, activator protein-1; CML, chronic myeloid leukemia; ES, embryonic stem; M-CSF, macrophage colony–stimulating factor; MMP-9, matrix metalloproteinase-9; RANKL, receptor activator of NFκB ligand; TRAP, tartrate-resistant acid phosphatase.
Lukas Kenner, Astrid Hoebertz, F. Timo Beil, Niamh Keon, Florian Karreth, Robert Eferl, Harald Scheuch, Agnieszka Szremska, Michael Amling, Marina Schorpp-Kistner, Peter Angel, Erwin F. Wagner; Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects . J Cell Biol 16 February 2004; 164 (4): 613–623. doi: https://doi.org/10.1083/jcb.200308155
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