Fatty Acids and Oxylipins in Osteoarthritis and Rheumatoid Arthritis—a Complex Field with Significant Potential for Future Treatments

Abstract

Purpose of Review Osteoarthritis (OA) and rheumatoid arthritis (RA) are characterized by abnormal lipid metabolism manifested as altered fatty acid (FA) profiles of synovial fluid and tissues and in the way dietary FA supplements can influence the symptoms of especially RA. In addition to classic eicosanoids, the potential roles of polyunsaturated FA (PUFA)-derived specialized pro-resolving lipid mediators (SPM) have become the focus of intensive research. Here, we summarize the current state of knowledge of the roles of FA and oxylipins in the degradation or protection of synovial joints. Recent Findings There exists discordance between the large body of literature from cell culture and animal experiments on the adverse and beneficial effects of individual FA and the lack of effective treatments for joint destruction in OA and RA patients. Saturated 16:0 and 18:0 induce mostly deleterious effects, while long-chain n-3 PUFA, especially 20:5n-3, have positive influence on joint health. The situation can be more complex for n-6 PUFA, such as 18:2n-6, 20:4n-6, and its derivative prostaglandin E2, with a combination of potentially adverse and beneficial effects. SPM analogs have future potential as analgesics for arthritic pain. Summary Alterations in FA profiles and their potential implications in SPM production may affect joint lubrication, synovial inflammation, pannus formation, as well as cartilage and bone degradation and contribute to the pathogeneses of inflammatory joint diseases. Further research directions include high-quality randomized controlled trials on dietary FA supplements and investigations on the significance of lipid composition of microvesicle membrane and cargo in joint diseases.

Synovial Extracellular Vesicles: Structure and Role in Synovial Fluid Tribological Performances

“…Until now, most of the research work in synovial lipids was divided into two fields: (1) a medical one, with the very detailed analysis of lipid composition [ 39 , 42 , 43 , 44 , 58 ], which showed an alteration of phospholipids in pathological states, but did not analyze the structure, nor the rheological consequences of such modifications, and (2) a biomimetic field [ 20 , 22 , 29 ], which is interested in the vesicular structures in relation to the lubrication process. Our work tried to match both fields and has established, directly from healthy and pathological samples, that it is not the intrinsic membrane structures or the lipid composition that matters for the rheology of the synovial fluid, but more the lipids over proteins and PL over total lipids ratios that causes the destructuring of the synovial vesicles, and eventually decreases the lubricating properties of the synovial fluid.…”

Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes

“…PGE 2 can induce deleterious and beneficial effects on synovial fibroblasts. In RA, it has been demonstrated to both stimulate and inhibit the overgrowth of synovial tissue [ 24 ].…”

“…As FLS EVs may alleviate OA or contribute to its pathogenesis, it would be important to characterize the FA composition of these particles. FAs have the potential to induce a plethora of beneficial and detrimental actions on different joint tissues [ 24 ], and their composition in EVs can influence the stability of EV membranes as well as reflect the availability of precursors for transcellular biosynthesis of LMs [ 23 ]. The aims of the present study were ( i ) to examine the HA and EV secretion by normal FLSs, ( ii ) to determine the expression of related genes, and ( iii ) to characterize the FA composition of FLS EVs, all in a temporal pattern during cell proliferation.…”

The Effect of Acknowledged and Novel Anti-Rheumatic Therapies on Periodontal Tissues—A Narrative Review

“…RA is outlined by a disregulation of the lipid metabolism that manifests as a modified profile of fatty acids in tissues and synovial fluid, and since dietary fatty acid supplements can alleviate the symptoms of RA patients, eicosanoids and polyunsaturated fatty acid-derived pro-resolving lipid mediators have been a highlight of recent research [95]. Extracellular vesicles have been regarded as most attractive as they have the capability of repairing damaged cartilage in animal models [96].…”