Activation of circulating monocytes by low-density lipoprotein—a risk factor for osteoarthritis?

Abstract

Synovial macrophages are key mediators of OA pathology, and skewing of macrophage phenotype in favour of an M1-like phenotype is thought to underlie the chronicity of synovial inflammation in OA. Components of the metabolic syndrome (MetS), such as dyslipidaemia, can affect macrophage phenotype and function, which could explain the link between MetS and OA development. Recently published studies have provided novel insights into the different origins and heterogeneity of synovial macrophages. Considering these findings, we propose an important role for monocyte-derived macrophages in particular, as opposed to yolk-sac derived residential macrophages, in causing a pro-inflammatory phenotype shift. We will further explain how this can start even prior to synovial infiltration; in the circulation, monocytes can be trained by metabolic factors such as low-density lipoprotein to become extra responsive to chemokines and damage-associated molecular patterns. The concept of innate immune training has been widely studied and implicated in atherosclerosis pathology, but its involvement in OA remains uncharted territory. Finally, we evaluate the implications of these insights for targeted therapy directed to macrophages and metabolic factors.

The association between lipid biomarkers and osteoarthritis based on the National Health and Nutrition Examination Survey and Mendelian randomization study

“…LDL is a cholesterol-rich lipoprotein. Kruisbergen et al found that LDL activation of circulating monocytes was a risk factor for OA 41 ; Oliviero et al found higher levels of serum LDL in patients with OA in comparison to controls 42 ; Mishra et al found higher LDL in the OA group than in the control group 43 . However, the results of this type of study are contrary to the results of the present study.…”