Expression of caspase-3 and -9 relevant to cartilage destruction and chondrocyte apoptosis in human osteoarthritic cartilage.
To clarify the involvement of the caspase family in the pathway of NO-induced chondrocyte apoptosis, osteoarthritis (OA) cartilage obtained from 8 patients undergoing total hip arthroplasty were used for histopathological study. Cartilage samples taken from non-fibrillated areas of femoral head resected during surgery for femoral neck fracture were used for comparison. DNA fragmentation of chondrocytes was detected by the nick end-labeling (TUNEL) method. Apoptosis was further confirmed by transmission electron microscopy. The distributions of nitrotyrosine (NT), caspase-3, and -9 were examined immunohistochemically. The populations of apoptotic as well as NT-, caspase-3-, and -9-positive cells were quantified by counting the number of cells in the superficial, middle, and deep layers, respectively. The TUNEL-positive cells were observed primarily in superficial proliferating chondrocytes, clustering chondrocytes, and deep-layer chondrocytes of OA cartilage. Few positive cells were seen in the proliferating chondrocytes in the middle layer. Positive reactions for caspase-3 and -9 were observed in chondrocytes in similar areas. Histological OA grade showed significant correlations with the mean populations of apoptotic chondrocytes (% apoptosis) over the 3 areas. The populations of NT-positive cells (% NT) over the same areas also showed significant correlation with OA grade. Positivity for caspase-3 closely correlated with the OA grade, % apoptosis and %NT. It was concluded that caspase-3 and -9 could play a role in NO-induced chondrocyte apoptosis in OA cartilage.
Matsuo
M
M
Department of Orthopaedic Surgery, Okayama University Medical School, Japan.
Nishida
K
K
Yoshida
A
A
Murakami
T
T
Inoue
H
H
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D019902:Chondrocytes / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008854:Microscopy, Electron; D008875:Middle Aged; D010003:Osteoarthritis / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
C002744:3-nitrotyrosine; D014443:Tyrosine; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases