Effect of hyaluronan on chondrocyte apoptosis and nitric oxide production in experimentally induced osteoarthritis.
OBJECTIVE
Nitric oxide (NO) plays an important role in cartilage degeneration, and NO donors induce chondrocyte apoptosis. This study evaluated the effect of intraarticular injections of hyaluronan (HA) on chondrocyte apoptosis and NO production using an experimental osteoarthritis (OA) model.


METHODS
Thirty-six New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT), and were divided into 3 groups. Four weeks after ACLT, the HA group started intraarticular HA injections once a week for 5 weeks; the vehicle group started to receive the carrier of HA; the no injection group received no treatment. All ACLT knees were harvested at Week 9 and evaluated for OA severity. Culture supernatants of the cartilage were analyzed for nitrite concentration. Cartilage sections were analyzed by TUNEL for apoptosis and by immunohistochemistry for nitrotyrosine.


RESULTS
OA in the HA group was less severe than the other 2 groups. The number of apoptotic chondrocytes was significantly lower in the HA group. HA injection did not influence NO production in cartilage.


CONCLUSIONS
HA protects against chondrocyte apoptosis during the development of OA, while it may not have definite effects on NO production in the joints. These inhibitory effects of HA on chondrocyte apoptosis may play a role in its mechanism of action in chondroprotection.
Department of Orthopaedics, University of California San Diego, 92093-0630, USA.
K
K
Takahashi
S
S
Hashimoto
T
T
Kubo
Y
Y
Hirasawa
M
M
Lotz
D
D
Amiel
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D009569:Nitric Oxide / Q000096:biosynthesis*; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D006820:Hyaluronic Acid