Rheumatoid arthritis (RA) mainly attacks synovial joints. In rheumatoid arthritis there is inflammation of the synovial membrane (which lines the joints), and is characterized by swelling and stiffness of the joint – stiffness is especially evident in the morning. Over time, as the disease progresses, joint range of motion is impaired and joints (e.g. finger joints) can become deformed and twisted. Like osteoarthritis, the inflammation in the joint is a major factor in the degradation of the articular cartilage.
Synovial Fibroblasts Play Key Role in Progression of RA and Joint Destruction Synovial fibroblasts line the synovial membrane which occurs at the joint and facilitates flexibility of joint movement. The synovial membrane provides separation between the more solid structures surrounding the joint, such as muscle. The synovial membrane also secrets a lubricating fluid called synovial fluid and provides packaging to contain the synovial fluid.
In rheumatoid arthritis, the pathological progression of the disease ultimately leads to the destruction of the joint. RA is a chronic inflammatory disease which starts with abnormalities in the synovial membrane, which becomes irritated, inflamed and thickened. The thickening of the synovial membrane is due to hyperplasia of the synovial fibroblasts, which are transformed into a type which is aggressive and destructive to the joint. Hyperplasia occurs, in part, due to decreased apoptosis or cellular death of the synovial fibroblasts. These are termed ACTIVATED – OR - STIMULATED SYNOVIAL FIBROBLASTS. Synovial fibroblasts become activated by inflammatory cytokines. (12, 13, 14)
• Activated Synovial Fibroblasts are the primary source of inflammation and cartilage destruction.
Pathological effects of Activated Synovial Fibroblasts:
1. Attach to articular cartilage and deeply invade the extracellular cartilage matrix.
2. Propagates the inflammatory immune response from the synovial membrane.
3. Increases levels of Matrix Degrading Enzymes, which accelerate cartilage destruction.
Synovial Fibroblasts: Natural Antagonists
Studies illustrate the ability of apigenin luteolin and curcumin to attenuate the pathological progression of rheumatoid arthritis. The hyperplasia of the synovial fibroblasts is significant because it represents diseased tissue which is a source of joint destroying activity.
• Apigenin: Induces apoptosis (cellular death) of the synovial fibroblast hyperplasia layer.(15)
• Luteolin: Inhibits hyperplasia (proliferation of synovial fibroblasts) and blocks many of the pathological actions of synovial fibroblasts.(16)
• Curcumin: Inhibits growth and induces apoptosis of synovial fibroblasts. Decreased expression of COX-2 and inhibition of prostaglandin E(2). Both are inflammatory secretion from synovial fibroblasts. Researchers concluded that these results showed that “curcumin might identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts”.(17) One further study, using a model of RA development, determined that curcumin administered prior to the onset of symtoms, was able to prevent RA. (18)
• Andrographolide: Inhibits invasion of RA fibroblast-like synoviocytes (RA-FLSs) a key element in the progression of RA .(19)
(19) Li GF, et al. Andrographolide inhibits the migration, invasion and matrix metalloproteinase expression of rheumatoid arthritis fibroblast-like synoviocytes via inhibition of HIF-1α signaling. Life Sci. 2015 Jul 2