Adjuvant-induced Arthritis in the Metatarsophalangeal Joint of Rats: a Stereological Study

Abstract

Small joints are the primary target for rheumatoid arthritis (RA). However, few studies have investigated the quantitative aspects of these changes using a design-unbiased stereological method. Eight male Lewis rats were randomized to either an arthritis group (complete Freund's adjuvant at the base of the tail) or a control group (saline solution). After 28 days the 5th metatarsophalangeal joints (5MTP joint) were decalcified and embedded in methylmethacrylate. The fingers were systematically sectioned perpendicular to the joint cartilage surface to produce 10-12 vertical sections. We quantified the morphological changes in four steps: (i) determination of the Cavalieri volume of joints, (ii) ascertainment of the volume density of tissues, (iii) estimation of the cartilage surface area, and (iv) 3-D counting of chondrocytes and mast cells. Arthritic joints were edematous due to a significant increase in the periarticular region. Synovium volume was inversely related to synovial space. Stereological analysis provided details of changes induced by chronic inflammation, particularly edema, synovial space narrowing, synovitis, mast cell recruitment, bone remodeling, and chondrocyte loss in 5MTP joints. These interrelated pathological changes in chronic inflammation collectively contribute to the progressive joint damage and dysfunction seen in arthritis.