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Specialized Pro-Resolving Mediators (SPMs) and Osteoarthritis (OA)

Osteoarthritis (OA) and rheumatoid arthritis (RA) are both inflammatory disorders that affect the cartilage and the lining of the joints, respectively. The Cleveland Clinic indicates that osteoarthritis is the most prevalent form of arthritis in the United States. It affects more than 70% of adults between 55 and 78 years of age, more commonly affecting women than men. The earliest symptoms of OA are joint stiffness, pain, and swelling. It is most common in the knee, hip, spine, and hands. Activity and weight bearing typically exacerbate pain.

Inflammation in Osteoarthritis & Comorbid Diseases

The Mayo Clinic explains that osteoarthritis “occurs when the protective cartilage on the ends of [the] bones wears down over time,” often with age. This definition and conception of OA as a “wear and tear” disease has been updated, however, following extensive progress in molecular biology research of the disease. Specifically, “the discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an inflammatory theory,” later confirmed by experimental data. Synovitis, the inflammation of the synovial membrane, is now recognized as characteristic in many OA patients. Inflammatory mediators released by cartilage, bone, and synovial fluid contribute to the inflammation that is prevalent in OA. Low-grade inflammation caused by metabolic syndrome and inflammaging may also contribute to OA.

Inflammation in OA is also associated with other chronic inflammatory conditions. For example, a study of middle-aged adults in the Netherlands found significant associations between OA of the knee and atherosclerosis. While most studies of the association between OA and cardiovascular disease are cross-sectional, evidence indicates that the diseases are “at least concurrent.” The low-level chronic inflammation that is common between both diseases indicate that developing one of them may influence the development of the other, particularly among women over 55 years of age.

Interestingly, a randomized controlled trial of patients with both depression and arthritis found that improvements in depression care also reduced pain and improved functional status. Depression is also an inflammatory condition and may develop through some of the same mechanisms as OA.

Managing Inflammation with Lifestyle and SPMs

There is strong evidence for the role of specialized pro-resolving mediators (SPMs) in resolving inflammation of the joints that is the hallmark of OA. Receptors for SPMs, such as leukotriene B4 receptor (BLT1), formyl peptide receptor 2 (FPR2), and chemokine like receptor 1 (CMKLR1) are present in synovial fluid.

Furthermore, researchers hypothesized that the underlying cause of inflammation present in OA could be the failure of pro-resolving mediators to activate in the joints. They collected the synovial fluid from arthritis patients and measured a variety of biomarkers, including SPM levels, their pathway markers, and levels of poly-unsaturated fatty acids. While there were higher levels of SPM precursors were present in OA patients when compared to RA patients, both diseases involved higher levels of pro-inflammatory cytokines compared to normal levels.

The symptoms of osteoarthritis may be managed with healthy lifestyle behaviors. For example, getting regular physical activity, maintaining a healthy weight, and eating an anti-inflammatory diet may slow the progression of the disease. It cannot be reversed, though, so the goal of treatment is typically pain relief and maintenance of function.  Adding SPMs to a healthy lifestyle, including maintaining a healthy weight, may help to ameliorate the symptoms of OA.


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