Endocrine Abstracts

Selenium (Se) is an essential trace element and is important for maintaining health and preventing disease. Se exhibits its biological function as the 21st proteinogenic amino acid selenocysteine (Sec). Different cis and trans acting factors are necessary for incorporation of Sec into proteins. Se can be transported and stored as Sec in selenoprotein P (SePP), a liver-derived protein which contains up to 10 Sec residues per protein in humans. Thus, SePP functions as both a systemic Se-transporter and a local Se-storage protein.

There are several hints demonstrating that Se and selenoproteins have an impact on bone physiology. Mutations in the Sec insertion sequence binding protein 2 (SBP2) and nutritional Se deficiencies are known to induce growth retardation in human patients and rats, respectively. Bone mineral content (BMC) and bone mineral density (BMD) have been shown to depend on the Se status in rodents. In humans, Se deficiency is known to be associated with Kashin-Beck disease, an endemic osteoarthropathy.

Since SePP is the central factor controlling Se status, we investigated SePP mRNA and the importance of SePP gene expression for bone physiology. In mice, SePP mRNA was strongly expressed in the developing limb buds. For functional analysis, SePP wildtype and SePP knockout mice were fed with regular diet and their tibia were analyzed by micro computer tomography (μCT). In male SePP-KO mice, the ratio of mineralized bone volume per total bone volume (BV/TV) was significantly reduced to 60% of wildtype. We conclude that impaired SePP expression results in reduced Se concentrations in the developing bone leading to impaired bone formation in male mice. Whether these results also apply for female mice or for humans remains to be investigated.