Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis.
OBJECTIVE
To examine the occurrence of apoptosis in human osteoarthritis (OA) cartilage, and to determine its relationship to cartilage degradation.


METHODS
Knee cartilage was obtained from subjects at autopsy, from a tissue bank, and from OA patients undergoing total joint replacement surgery. Chondrocytes were isolated and the number of apoptotic cells was analyzed by flow cytometry. Apoptotic cells in cartilage sections were identified by the detection of DNA strand breaks. Electron microscopy was applied to demonstrate morphologic changes, and Safranin O staining was performed to analyze the relationship between apoptosis and proteoglycan depletion.


RESULTS
Flow cytometry on cell suspensions prepared from collagenase digests of cartilage showed that approximately 22.3% of OA chondrocytes and 4.8% of normal chondrocytes were undergoing apoptosis. Staining of cartilage sections demonstrated the presence of apoptotic cells in the superficial and middle zones. Cartilage areas that contained apoptotic cells showed proteoglycan depletion, and the number of apoptotic cells was significantly correlated with the OA grade.


CONCLUSIONS
These observations demonstrate increased chondrocyte apoptosis in OA cartilage. Chondrocyte apoptosis and proteoglycan depletion are anatomically linked and may be mechanistically related.
Hashimoto
S
S
The Scripps Research Institute, La Jolla, California 92037, USA.
Ochs
R L
RL
Komiya
S
S
Lotz
M
M
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D019902:Chondrocytes / Q000378:metabolism / Q000648:ultrastructure*; D005434:Flow Cytometry; D006801:Humans; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*