Regulating ΔFosB expression in adult tet-off-ΔFosB transgenic mice alters bone formation and bone mass

The ΔFosB isoforms are naturally occurring AP-1 family members that increase bone volume via a cell-autonomous effect on osteoblastic bone formation. Mice overexpressing ΔFosB demonstrate a very high level of bone formation, resulting in a progressive osteosclerosis. Despite the linkage of bone formation and resorption in physiological systems, no alteration in bone resorption was detected in mice overexpressing ΔFosB. To determine whether altering ΔFosB expression can regulate bone formation independently of bone resorption in adult mice, we used the Tet-Off-inducible transgene system to induce or block transgenic ΔFosB overexpression and thereby regulate bone formation in vivo. Overexpression of ΔFosB after skeletal maturity increased trabecular bone volume by increasing bone formation, again without altering bone resorption, indicating that developmental ΔFosB overexpression is not required for the osteosclerotic phenotype. Similarly, switching off ΔFosB overexpression after osteosclerosis had developed led to a marked decrease in bone formation and loss of bone mass such that trabecular bone volume approached normal levels. Despite this dramatic reduction, no alteration in bone resorption was detected. These results clearly demonstrate that ΔFosB regulates bone formation and bone mass in adult mice with no effect on bone resorption.