Obesity, Inflammation, and Immune System in Osteoarthritis

Abstract

Obesity remains the most important risk factor for the incidence and progression of osteoarthritis (OA). The leading cause of OA was believed to be overloading the joints due to excess weight which in turn leads to the destruction of articular cartilage. However, recent studies have proved otherwise, various other factors like adipose deposition, insulin resistance, and especially the improper coordination of innate and adaptive immune responses may lead to the initiation and progression of obesity-associated OA. It is becoming increasingly evident that multiple inflammatory cells are recruited into the synovial joint that serves an important role in pathological changes in the synovial joint. Polarization of macrophages and macrophage-produced mediators are extensively studied and linked to the inflammatory and destructive responses in the OA synovium and cartilage. However, the role of other major innate immune cells such as neutrophils, eosinophils, and dendritic cells in the pathogenesis of OA has not been fully evaluated. Although cells of the adaptive immune system contribute to the pathogenesis of obesity-induced OA is still under exploration, a quantity of literature indicates OA synovium has an enriched population of T cells and B cells compared with healthy control. The interplay between a variety of immune cells and other cells that reside in the articular joints may constitute a vicious cycle, leading to pathological changes of the articular joint in obese individuals. This review addresses obesity and the role of all the immune cells that are involved in OA and summarised animal studies and human trials and knowledge gaps between the studies have been highlighted. The review also touches base on the interventions currently in clinical trials, different stages of the testing, and their shortcomings are also discussed to understand the future direction which could help in understanding the multifactorial aspects of OA where inflammation has a significant function.

Keywords: T cells; adaptive immunity; biomechanics; innate immunity; obesity; osteoarthritis; synovium & osteoarthritis.

Figure 1

Schematic diagram shows the immune cell being up and downregulated in lean and overweight/obese individuals. The cells on the left represent the lean physiological aspects of the immune system and on the right, the obese immune system (24). In lean population during inflamed condition the macrophages M1 cells are lower in comparison to M2 cells. However, the reverse is seen in the obese inflammation. Lymphoblastic cells like Th1, Th17, T helper, and B cells are lower in comparison with Treg cells and NK cells in lean inflammation population. However, in obese population, there is an increase in the production of Th1, Th17, T helper cells, B cells but reduction in the number of T reg cells and NK becomes low. Granulocytes like the eosinophiles are higher in comparison with neutrophiles in lean inflammation condition, however, the reverse is observed with obese population in their inflammatory condition.

Figure 2

Schematic representation of the immune cells and their products in hypoxia condition. From left, the expression of neutrophiles cells multiplies. The expression of M1 macrophages increases and M2 macrophages decreases. The total number of NK cells goes up which in turn increases the glycolytic metabolism. The number of Th17 cells goes up. B cells also increases along with high regulation of antibodies. Th1 cells and T reg cells production decreases due to low oxygen. The number T cytotoxic cells also decrease because of reduced oxygen. The number of DCs increases which intern increases the production of chemokines associated with DCs.