Involvement of nitric oxide in chondrocyte cell death in chondro-osteophyte formation.
OBJECTIVE
To examine the nitric oxide (NO) production relevant to chondrocyte cell death in order to elucidate the mechanism of chondro-osteophyte formation in osteoarthrotic joints.


METHODS
Human chondro-osteophytes were obtained during total hip arthroplasty. Expression of inducible nitric oxide synthase (iNOS) mRNA was determined by in-situ hybridization. Localization of iNOS and nitrotyrosine at protein level were examined by immunohistochemistry. Cell death of chondrocytes were confirmed by both TUNEL method and transmission electron microscopy.


RESULTS
The various populations of proliferative and hypertrophic chondrocytes expressed iNOS mRNA and iNOS as well as nitrotyrosine protein. Approximately 30% of hypertrophic chondrocytes forming chondro-osteophyte showed positive reaction to TUNEL staining. Electron microscopy confirmed both disintegrated and apoptotic chondrocytes in these zones. In the deep hypertrophic zone calcification was seen around each of the matrix vesicles and some masses of cell debris.


CONCLUSIONS
Chondro-osteophyte formation involves NO production by chondrocytes. The expression and localization of iNOS and nitrotyrosine in chondro-osteophytes suggest the significant role of NO in chondrocyte hypertrophy and apoptosis.
Nishida
K
K
Department of Orthopaedic Surgery, Faculty of Medicine, Okayama University Medical School, Japan. knishida@po.harenet.ne.jp
Doi
T
T
Matsuo
M
M
Ishiwari
Y
Y
Tsujigiwa
H
H
Yoshida
A
A
Shibahara
M
M
Inoue
H
H
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D019902:Chondrocytes / Q000378:metabolism*; D015331:Cohort Studies; D006621:Hip Joint / Q000473:pathology; D006801:Humans; D006984:Hypertrophy; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D015207:Osteoarthritis, Hip / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D012333:RNA, Messenger; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II