Oxidized low-density lipoprotein promotes osteoclast differentiation from CD68 positive mononuclear cells by regulating HMGB1 release.

Patients with ankylosing spondylitis (AS) have an increased risk for cardiovascular mortality. The circulating ox-LDL/LDL ratio is associated with subclinical atherosclerosis in patients with systemic lupus erythematosus. In this study, we found that the ox-LDL/LDL ratio was increased in AS patients. The levels of serum RANKL and HMGB1 were also elevated in AS patients, and the number of CD68+/RANK+ cells was increased in peripheral blood from AS patients. 0.03% ox-LDL in LDL, similar to the ox-LDL/LDL ratio in peripheral blood from AS patients, promoted cytoplasmic translocation and release of HMGB1 as well as RANK expression. Further investigation evidenced that ox-LDL-induced EGR1 expression contributed to the cytoplasmic translocation of HMGB1 and CD68 assisted the secretion of HMGB1 from cytoplasm to extracellular matrix. Extracellular HMGB1 induced RANK expression in CD68+ mononuclear cells, forming osteoclast precursors that were differentiated to osteoclasts in response to RANKL. Taken together, these results suggested that the changes, including ox-LDL/LDL ratio, CD68+/RANK+ cells number, and the levels of RANKL and HMGB1 in AS patients, favored osteoclastogenesis.