Apoptotic chondrocyte death in human osteoarthritis

Objective. To define apoptotic chondrocyte death and the expression of Bcl- 2, Bax, and Fas in human osteoarthritis (OA) cartilage. Methods. Cartilage samples were obtained from patients with knee OA at the time of joint replacement surgery and from normal autopsy cases. in OA, sec tions were obtained both from the lesional area, usually within 1 cm of bon y exposure, and from the non-lesional area, which had macroscopically norma l appearance or only mild surface irregularities. Apoptosis was verified by microscopic examination of hematoxylin and eosin stained specimens, TUNEL staining, electron microscopy, and DNA ladder analysis by electrophoresis. Immunohistochemistry was done to study the expression of Bcl-2, Bax, and Fa s, Apoptotic cells and Bcl-2, Bax, and Fas positive cells were counted with in defined microscopic fields. Expression of Bcl-2 and Bax was verified by Western blot. Results. The percentage of apoptotic cells in the lesional area was signifi cantly higher than in the nonlesional area in cartilage from the same patie nt with OA, while apoptotic cells were rarely seen in normal cartilage. Thi s result was confirmed by TUNEL stain. Many chondrocytes with chromatin con densation were verified in electron microscopy, and DNA from OA lesional ca rtilage revealed a DNA ladder on electrophoresis. Bcl-2 and Fas expressions were significantly higher in the OA lesional area than in the non-lesional area. On the other hand, Bcl-2 expression in normal cartilage was signific antly higher than in OA cartilage. There was no significant difference in B ax expression among normal, OA lesional, and OA non-lesional cartilage. Conclusion. These results show that apoptotic chondrocyte death occurs more frequently in OA compared to normal cartilage and in OA lesional compared to OA non-lesional cartilage. The different expression patterns of Bcl-2 an d Fas in OA lesional and non-lesional cartilage suggest that they might be involved in the pathogenesis of OA.