The increased bone mass in deltaFosB transgenic mice is independent of circulating leptin levels.
Transgenic mice overexpressing deltaFosB, a naturally occurring splice variant of FosB, develop an osteosclerotic phenotype. The increased bone formation has been shown to be due, at least in part, to autonomous effects of deltaFosB isoforms on cells of the osteoblast lineage. However, abdominal fat and marrow adipocytes are also markedly decreased in deltaFosB mice, leading to low serum leptin levels. Increased bone mass has been linked to the absence of leptin and leptin receptor signaling in ob/ob and db/db mice. Thus, in addition to affecting directly osteoblastogenesis and bone formation, deltaFosB isoforms might increase bone mass indirectly via a decrease in leptin. To test this hypothesis, we restored normal circulating levels of leptin in deltaFosB mice via sc implanted osmotic pumps. Complete histomorphometric analysis demonstrated that trabecular bone volume as well as dynamic parameters of bone formation was unchanged by this treatment in both deltaFosB transgenic mice and control littermates. This demonstration that restoring circulating levels of leptin in deltaFosB transgenic mice failed to rescue the bone phenotype further indicates that the marked increase in bone formation is autonomous to the osteoblast lineage.
Kveiborg
M
M
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Chiusaroli
R
R
Sims
N A
NA
Wu
M
M
Sabatakos
G
G
Horne
W C
WC
Baron
R
R
D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000033:anatomy & histology*; D020738:Leptin / Q000097:blood* / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000502:physiology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
D020738:Leptin; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; D019000:Phosphotyrosine