Apoptotic cell death is not a widespread phenomenon in normal aging and osteoarthritic human articular knee cartilage - A study of proliferation, programmed cell death (apoptosis), and viability of chondrocytes in normal andosteoarthritic human knee cartilage

Objective. Chondrocytes are crucial for adequate matrix balance and functio n. Cell proliferation and, recently, extensive apoptotic cell death have be en reported in osteoarthritic (OA) cartilage. Apoptotic cell death would be an obvious central factor in the initiation and progression of OA, since t here is no potential for replacing articular chondrocytes in the adult. The refore, we studied the occurrence of apoptotic cell disintegration and cell proliferation in OA and normal articular cartilage obtained from the knees of adult donors of all ages. Methods. Following immunostaining for cellular proteins as well as staining for nuclear DNA, we performed triple-channel confocal laser scanning micro scopy on thick cartilage slices to evaluate lacunar emptying and cell viabi lity. Cell proliferation and apoptotic cell death were evaluated morphologi cally, by immunodetection of the proliferation-associated Ki-67 antigen, an d by the TUNEL reaction. Results. With the exception of the calcified layer, we were not able to det ect any major (apoptotic or nonapoptotic) cell disintegration in normal you ng or aged articular knee cartilage. Single apoptotic cells were detected i n OA articular knee cartilage. A significant increase in lacunar emptying w as observed in late-stage specimens with higher Mankin scores compared with age-matched normal control cartilage specimens, but not in low-grade lesio ns. A significant (but lesser) increase in empty lacunae was also observed with age in normal cartilage. Cell proliferation was rarely detected in OA cartilage samples and was not detected at all in normal cartilage samples. Conclusion. Our results confirm the findings of previous studies showing th at cell proliferation occurs in OA cartilage. They also show that, contrary to previous suggestions, apoptotic cell death is not a widespread phenomen on in aging or OA cartilage.