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The Increased Bone Mass in FosB Transgenic Mice Is Independent of Circulating Leptin Levels

Departments of Cell Biology and Orthopedics, Yale University School of Medicine, New Haven, Connecticut 06510

Address all correspondence and requests for reprints to: Dr. Roland Baron, Department of Orthopedics and Cell Biology, Yale University, School of Medicine, 333 Cedar Street, SHM IE-55, New Haven, Connecticut 06510. E-mail: roland.baron{at}yale.edu.

Transgenic mice overexpressing FosB, 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 FosB isoforms on cells of the osteoblast lineage. However, abdominal fat and marrow adipocytes are also markedly decreased in FosB 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, FosB isoforms might increase bone mass indirectly via a decrease in leptin. To test this hypothesis, we restored normal circulating levels of leptin in FosB 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 FosB transgenic mice and control littermates. This demonstration that restoring circulating levels of leptin in FosB transgenic mice failed to rescue the bone phenotype further indicates that the marked increase in bone formation is autonomous to the osteoblast lineage.

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