Selenoprotein P is the essential selenium transporter for bones

Area of Science:

• Biochemistry
• Bone Biology
• Nutritional Science

Background:

• Selenium (Se) is vital for bone physiology, evidenced by Kashin-Beck disease, an Se-dependent osteoarthritis.
• Mutations in SECIS binding protein 2 (SBP2) impair selenoprotein biosynthesis and delay bone development.
• The role of circulating selenoprotein P (SePP) in bone homeostasis remains unclear.

Purpose of the Study:

• To investigate the function of SePP in bone homeostasis.
• To determine the mechanism of selenium transport to bones.
• To explore potential feedback mechanisms in Se metabolism.

Main Methods:

• Analysis of murine models with altered Se metabolism.
• Assessment of selenoprotein gene and biosynthesis factor expression in bones.
• Measurement of Se concentrations in serum and bone.
• Evaluation of SePP receptor expression (Lrp8, Lrp2) in bones.
• Generation of SePP-transgenic mice with cell-specific expression in hepatocytes.

Main Results:

• Selenoprotein genes and biosynthesis factors are expressed in bones, with bone Se localized to the organic matrix.
• Sepp-knockout mice showed a 25-fold decrease in serum Se but only a 2.5-fold decrease in bone Se.
• Hepatocyte-specific SePP expression restored bone Se levels in knockout mice.
• Lrp8, a SePP receptor, was found in bones and its mRNA increased in Sepp-knockout mice.
• Lrp2 was absent in bones.

Conclusions:

• SePP is the essential Se transporter to bones.
• A novel feedback mechanism enhances Se uptake in Se-deprived bones.
• Findings contribute to understanding hepatic osteodystrophy and bone phenotypes in selenoprotein biosynthesis disorders.