Oxidation-specific epitopes restrain bone formation

doi:10.1038/s41467-018-04047-5

Oxidation-specific epitopes restrain bone formation

2018-06-06

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DOI：10.1038/s41467-018-04047-5

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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.

Keywords:

LOW-DENSITY-LIPOPROTEIN

OSTEOBLASTIC CELLS

SCAVENGER RECEPTORS

APOPTOTIC CELLS

AORTIC CALCIFICATION

RANKL EXPRESSION

INNATE IMMUNITY

OXIDIZED LDL

ATHEROSCLEROSIS

ANTIBODIES

Oxidation-specific epitopes restrain bone formation

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