Effect of hyaluronan on chondrocyte apoptosis and nitric oxide production in experimentally induced osteoarthritis

J Rheumatol. 2000 Jul;27(7):1713-20.


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.

Conclusion: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anterior Cruciate Ligament / surgery
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cartilage / drug effects
  • Cartilage / metabolism
  • Cartilage / pathology
  • Cell Count
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Hyaluronic Acid / pharmacology*
  • Knee Joint / drug effects
  • Knee Joint / pathology
  • Knee Joint / surgery
  • Nitric Oxide / biosynthesis*
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / pathology
  • Osteoarthritis, Knee / physiopathology
  • Rabbits
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism


  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Hyaluronic Acid