Over the past 40 years rheumatoid arthritis (RA) has been the subject of extensive immunological and histological investigations. Rheumatoid synovial tissues, obtained from synovectomy, joint arthroplasty or biopsy have been examined by various pathologists and researchers using a range of ever more sophisticated techniques. From conventional histology using haematoxylin and eosin, to immunolocalisation, in situ hybridisation, and more recently to the use of extracted RNA for specific gene analysis. From early studies describing synovial A and B cells as the major components of rheumatoid synovium, we now have a better understanding of T cell subsets, monocyte-macrophage populations, and the expression of disease related genes such as cytokines and proteinases. This knowledge undoubtedly provides a better understanding of the inflammatory processes that operate in rheumatoid synovial tissue; but the cardinal feature of RA is cartilage and bone degradation. Far fewer studies have been reported on these sites of cartilage erosion or bone loss, yet it is here that the catabolic processes responsible for joint destruction are manifest.

Our interest in the ‘rheumatoid lesion’, a term used to describe the cartilage-pannus junction or sites of cartilage erosion, started in 1976 with the finding of the enzyme collagenase at sites of cartilage loss.1 ,2 Since then we have examined numerous cartilage-pannus specimens derived from more than 150 different cases of knee joint surgery, using a variety of immunological and histochemical techniques to identify specific cell types and different matrix degrading enzymes. During these studies we have become aware of the broad range of histological findings and the variations in proteinase expression.3 ,4 As knowledge of the mechanisms responsible for joint destruction is essential for the development of preventative pharmacological treatments, this overview presents our observations on the complex cellular and enzymic processes involved in cartilage degradation and subchondral bone …