Relationship between chondrocyte apoptosis and matrix depletion in human articular cartilage

Objective. Chondrocyte apoptosis has been described in studies of the patho genesis of various arthritides. Since matrix degradation is important in th e pathology of arthritis, we investigated the effect of matrix depletion on chondrocyte apoptosis. Methods. Consecutive 1 mm sections of child's rib cartilage were cultured u nder 4 sets of conditions: (1) control; and treatment with (2) hyaluronidas e, (3) collagenase, (4) hyaluronidase/collagenase alternately. Sections wer e harvested on Days 5, 8, and 11, and the proportion of apoptotic cells was measured by propidium iodide staining and flow cytometry. Changes of Fas a nd Fas ligand expression were verified by immunohistochemistry and Western blot. Results. Collagenase treatment led to an increase of apoptosis, which began on Day 8, whereas hyaluronidase treatment had no effect on chondrocyte via bility up to Day 11. Alternating hyaluronidase and collagenase treatment in duced chondrocyte death earlier, but the difference in apoptotic rate was n ot significant on Days 8 or 11 compared to collagenase treatment alone. Imm unohistochemistry showed the expression of Fas ligand in all enzymatically treated specimens. Expression of Fas receptor was ubiquitous in both contro l and treated specimens. Conclusion. The collagen framework is important in the maintenance of chond rocyte survival in human cartilage. Upregulation of Fas ligand in matrix de pleted specimens suggested that the Fas pathway may have a role in apoptosi s induced by matrix depletion.