Rodent Preclinical Models for Developing Novel Antiarthritic Molecules: Comparative Biology and Preferred Methods for Evaluating Efficacy
Figure 6
Structural lesions of immune-mediated joint disease in arthritic rodents include both skeletal and soft tissue changes. Relative to nonarthritic control animals ((a) and (c)), young adult, male Lewis rats with the aggressive mycobacterial variant of adjuvant-induced arthritis (AIA-Myc) ((b) and (c)) develop extensive inflammation of the fatty periarticular soft tissues (F) and bone marrow, erosion of cortical and trabecular bone, loss of physeal (growth plate) cartilage (asterisks (*)), and exuberant production of periosteal bone (P). Fibrin, inflammatory cells, and (for CIA) pannus are additional features that may be evident on hematoxylin and eosin (H&E)-stained sections ((a) and (b)). Cartilage degeneration is demonstrated by toluidine blue staining ((c) and (d)), with the normal uniform dark purple labeling of surface and deep articular cartilage in nonarthritic controls (c) being replaced in inflamed joints by loss of staining in the superficial matrix of arthritic rats (d). Extensive loss of subchondral and trabecular bone (pale white plates and columns adjacent to cartilage) results from extensive infiltration of the bone marrow by inflammatory cells (punctate gray/green fields between bones in (d)). Abbreviations: N = navicular tarsal bone, Ta = talus, Ti = tibia.
