Formation and phenotype of cell clusters in osteoarthritic meniscus

Objective. To determine the histologic changes that accompany the formation of cell clusters during the early stages of osteoarthritis development in the meniscus, and to characterize the expression phenotype of these cells. Methods. Histologic sections of medial menisci from normal and anterior cru ciate ligament (ACL)deficient rabbit knees were immunolabeled with monoclon al antibodies for vimentin to highlight the cytoskeleton of meniscal cells, Ki-67 to identify proliferating cells, and type X collagen to evaluate cha nges in the cell expression phenotype. Tissue mineralization was assessed b y specific staining with alizarin red. Results. Following ACL transection, there was an alteration in the normal i nterconnected network of meniscal cells in the fibrocartilaginous region of the tissue. This led to isolation of islands of cells within the extracell ular matrix of the meniscal tissue. These islands of cells displayed 3 diff erent morphologies based on cell composition: 1) stellate cells, 2) stellat e as well as round cells, and 3) round cells. Islands composed solely of ro und cells were more prominent in the latter stages following ACL transectio n, and the size of these islands increased with time, apparently as the res ult of cell proliferation. These islands of cells corresponded to the "clus ters" previously described in osteoarthritic cartilage. Strong expression o f type X collagen colocalized with the deposition of calcium within the men iscal regions enriched with cell clusters. Conclusion. Based on the observed changes in cell distribution, morphology, and cell proliferation as well as the previous detection of apoptosis in s imilar studies of rabbit knee joints, we propose a model for the developmen t of cell clusters in the osteoarthritic meniscus. The morphologic appearan ce as well as the type X collagen expression phenotype of the meniscal cell s forming the clusters is similar to that of hypertrophic chondrocytes. The se findings provide a basis for understanding the origin of cell clusters i n other joint connective tissues, such as osteoarthritic cartilage.