Phospholipids and Sphingolipids in Osteoarthritis.

Many studies now emphasize the intricate relationship between lipid metabolism and osteoarthritis (OA), a leading cause of disability. This narrative review examines alterations in the levels of phospholipids (PLs) and sphingolipids (SLs) in synovial fluid (SF), plasma, serum, and articular tissues; discusses their role in joint lubrication, inflammation, and cartilage degradation; and describes their potential as diagnostic markers and therapeutic targets. Key findings include stage-dependent elevated levels of specific PLs and SLs in the SF, blood, and tissue of OA patients, implicating them as possible biomarkers of disease severity and progression. Studies suggest that beyond the involvement of these lipids in joint lubrication, individual species, such as lysophosphatidylcholine (LPC) 16:0, lysophosphatidic acid (LPA), ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P), contribute to pain, inflammation, and degradation of joints through various signaling pathways. Cross-species comparisons suggest that dogs and mice experience similar lipidomic changes during OA as humans, rendering them valuable models for studying lipid-related mechanisms. PLs and SLs in SF appear to originate primarily from the synovial blood capillaries through diffusion. In addition, lipids that are produced locally by fibroblast-like synoviocytes (FLSs) are influenced by cytokines and growth factors that regulate the biosynthesis of PLs for joint lubrication. Emerging research has identified genes such as UGCG and ESYT1 as regulators of lipid metabolism in OA. Further, we examine the suitability of lipids as biomarkers of OA and the potential of targeting the PL and SL pathways to treat OA, emphasizing the need for further research to translate these findings into clinical applications.