Hypothesis

Although rheumatoid arthritis (RA) is believed to be primarily an inflammatory disease of synovium, there is a good possibility that the initiation of the rheumatoid process is triggered by the autoimmune reaction involving type II collagen in the articular cartilage as a consequence of an unknown aetiological agent. Synovitis and other extra-articular features may be induced secondary to the immune complex formation in the subchondral area.

Extensive scientific data on the immune nature of RA have been accumulated.1 According to this, RA is considered to be an autoimmune disease that is presently incurable. Although its aetiology remains unknown, most investigators believe that RA is primarily an inflammatory disease of synovial membrane of the joints. However, here we show evidence that RA primarily involves articular cartilage and subchondral bone, not the synovium; this new direction of research may allow for the development of a specific treatment for the disease.

It is generally accepted that the initial events in the development of articular damage is the proliferation of synovial cells together with inflammation and vascular neoformation in the stroma of synovial tissue.2 As the disease progresses, the proliferating synovial tissue extends over the articular cartilage and erodes from the joint surface down to the subchondral bone. Eventually, small and large joints of the patient are destroyed, deformed and ankylosed.

Recently, we have focused on the following clinical facts that raise an important question: Is RA really a synovial disease? Firstly, although administration of non-steroidal anti-inflammatory drugs, anti-rheumatic medicines and corticosteroids is recognised as a fundamental conservative treatment for RA, these cannot completely suppress the synovitis of affected joints. Even after surgical synovectomy, the removal of inflammatory synovial tissue, most cases develop varying degrees of recurrent synovitis with time, and the progression in joint deterioration and deformity cannot be prevented.3-5 …