Oxidation-specific epitopes restrain bone formation

Elena Ambrogini (), Xuchu Que, Shuling Wang, Fumihiro Yamaguchi, Robert S. Weinstein, Sotirios Tsimikas, Stavros C. Manolagas, Joseph L. Witztum and Robert L. Jilka
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Elena Ambrogini: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System
Xuchu Que: University of California San Diego
Shuling Wang: University of California San Diego
Fumihiro Yamaguchi: University of California San Diego
Robert S. Weinstein: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System
Sotirios Tsimikas: University of California San Diego
Stavros C. Manolagas: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System
Joseph L. Witztum: University of California San Diego
Robert L. Jilka: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04047-5

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