page 613) show that JunB, which acts as one-half of an AP-1 dimer, is a positive regulator of both osteoblast and osteoclast proliferation and differentiation. In the process they have produced a new animal model for studying osteoporosis.
As JunB is essential for placenta formation, the authors conditionally deleted the gene in embryonic tissues. The resulting mice were viable, but soon developed severe bone loss resembling human senile osteoporosis, and later a condition resembling chronic myelogenous leukemia. A separate strain of mice, lacking JunB only in the macrophage and osteoclast lineage, but not in osteoblasts, developed severe osteopetrosis and increased bone mass.
The leukemia is consistent with earlier results suggesting a tumor–suppressor function for JunB, which negatively regulates the proliferation of myeloid progenitor cells. Osteoblast and osteoclast proliferation, however, seem to be boosted by JunB, and ex vivo experiments confirm that this effect is cell autonomous. Thus, JunB is a key regulator of bone growth and affects bone formation more strongly than resorption. ▪