Oxidation-specific epitopes restrain bone formation.

Abstract

Atherosclerosis and osteoporosis are epidemiologically linked and oxidation specific epitopes (OSEs), such as phosphocholine (PC) of oxidized phospholipids (PC-OxPL) and malondialdehyde (MDA), are pathogenic in both. The proatherogenic effects of OSEs are opposed by innate immune antibodies. Here we show that high-fat diet (HFD)-induced bone loss is attenuated in mice expressing a single chain variable region fragment of the IgM E06 (E06-scFv) that neutralizes PC-OxPL, by increasing osteoblast number and stimulating bone formation. Similarly, HFD-induced bone loss is attenuated in mice expressing IK17-scFv, which neutralizes MDA. Notably, E06-scFv also increases bone mass in mice fed a normal diet. Moreover, the levels of anti-PC IgM decrease in aged mice. We conclude that OSEs, whether produced chronically or increased by HFD, restrain bone formation, and that diminished defense against OSEs may contribute to age-related bone loss. Anti-OSEs, therefore, may represent a novel therapeutic approach against osteoporosis and atherosclerosis simultaneously.

• Authors: Elena Ambrogini, Xuchu Que, Shuling Wang, Fumihiro Yamaguchi, Robert S Weinstein, Sotirios Tsimikas, Stavros C Manolagas, Joseph L Witztum, Robert L Jilka
• Journal: Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 2193 (06 06 2018) ISSN: 2041-1723 [Electronic] England
• PMID: 29875355 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes
• Immunoglobulin M
• Lipoproteins, LDL
• Single-Chain Antibodies
• oxidized low density lipoprotein

Topics

• Animals
• Cell Proliferation (drug effects)
• Cells, Cultured
• Diet, High-Fat (adverse effects)
• Epitopes (genetics, immunology, metabolism)
• Immunoglobulin M (genetics, immunology)
• Lipoproteins, LDL (pharmacology)
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Osteoblasts (cytology, drug effects, immunology)
• Osteogenesis (genetics, immunology)
• Osteoporosis (etiology, genetics, immunology)
• Oxidation-Reduction
• Single-Chain Antibodies (genetics, immunology)