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Transgenic expression of a single\u2010chain variable fragment (scFv) of the antigen\u2010binding domain of E06, an IgM natural antibody that recognizes the phosphocholine (PC) moiety of OxPLs, increases trabecular and cortical bone in adult male and female mice by increasing bone formation. OxPLs increase with age, while natural antibodies decrease. Age\u2010related bone loss is associated with increased oxidative stress and lipid peroxidation and is characterized by a decline in osteoblast number and bone formation, raising the possibility that increased OxPLs, together with the decline of natural antibodies, contribute to age\u2010related bone loss. We show here that transgenic expression of E06\u2010scFv attenuated the age\u2010associated loss of spinal, femoral, and total bone mineral density in both female and male mice aged up to 22 and 24\u00a0months, respectively. E06\u2010scFv attenuated the age\u2010associated decline in trabecular bone, but not cortical bone, and this effect was associated with an increase in osteoblasts and a decrease in osteoclasts. Furthermore, RNA\u2010seq analysis showed that E06\u2010scFv increased Wnt10b expression in vertebral bone in aged mice, indicating that blocking OxPLs increases Wnt signaling. Unlike age\u2010related bone loss, E06\u2010scFv did not attenuate the bone loss caused by estrogen deficiency or unloading in adult mice. These results demonstrate that OxPLs contribute to age\u2010associated bone loss. Neutralization of OxPLs, therefore, is a promising therapeutic target for senile osteoporosis, as well as atherosclerosis and non\u2010alcoholic steatohepatitis (NASH), two other conditions shown to be attenuated by E06\u2010scFv in mice.<\/jats:p>","DOI":"10.1111\/acel.13442","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T03:21:08Z","timestamp":1626664868000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Neutralization of oxidized phospholipids attenuates age\u2010associated bone loss in mice"],"prefix":"10.1111","volume":"20","author":[{"given":"Michela","family":"Palmieri","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism Center for Osteoporosis and Metabolic Bone Diseases and Center for Musculoskeletal Disease Research University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System Little Rock AR 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