The role of oxidation of low-density lipids in pathogenesis of osteoarthritis: A narrative review

Abstract

Osteoarthritis (OA) is a chronic joint disorder that causes degeneration of cartilage, synovial inflammation, and formation of osteophytes. Aging, obesity, and sex are considered the main risk factors of OA. Recent studies have suggested that metabolic syndrome (MetS) disorders, such as hypertension, hyperlipidemia, diabetes mellitus, and obesity, may be involved in the pathogenesis and progression of OA. MetS disorders are common diseases that also result in atherosclerosis. Researchers believe that OA and atherosclerosis have underlying similar molecular mechanisms because the prevalence of both diseases increases with age. Oxidation of low-density lipoprotein (ox-LDL) is believed to play a role in the pathogenesis of atherosclerosis. Recent reports have shown that ox-LDL and low-density lipoprotein receptor 1 (LOX-1) are involved in the pathogenesis of OA. The purpose of this narrative review is to summarize the current understanding of the role of the LOX-1/ox-LDL system in the pathogenesis of OA and to reveal common underlying molecular pathways that are shared by MetS in OA and the LOX-1/ox-LDL system.

Keywords: Osteoarthritis; atherosclerosis; low-density lipoprotein; metabolic syndrome; oxidation; pathogenesis.

Figure 1.

Effects of LOX-1/ox-LDL interaction in articular chondrocytes. LOX-1, low-density lipoprotein receptor 1; ox-LDL, oxidation of low-density lipoprotein; NF-KB, nuclear factor kappa B; PPAR gamma, peroxisome proliferator-activated receptor γ; MCP-1, monocyte chemoattractant protein 1; PG, proteoglycan; ROS, reactive oxygen species; VEGF, vascular endothelial growth factor; COLX, type X collagen.

Figure 2.

Cycle of MetS in OA. This figure shows the oxidative environment in OA. MetS disorders, such as HT, HL, and DM, induce the release of inflammatory cytokines. Oxidative substances, such as ROS or ox-LDL, are then released, leading to degeneration of cartilage and synovitis. A lack of exercise due to pain also leads to obesity and this in turn further induces MetS. Such a vicious cycle is presumably caused by the oxidative stress environment in OA. MetS, metabolic syndrome; OA, osteoarthritis; HT, hypertension; HL, hyperlipidemia; DM, diabetes mellitus; ROS, reactive oxygen species; OA, osteoarthritis.