Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model

Ann Clin Lab Sci. 2015 Summer;45(4):426-32.

Abstract

Background: To investigate the effects of AOD9604 intra-articular injections with or without hyaluronic acid (HA) in a collagenase-induced knee osteoarthritis (OA) rabbit model.

Design: Mature New Zealand white rabbits (n=32) were randomly administered 2 mg collagenase type II twice in each knee joint. Weekly injections of 0.6 mL saline (Group 1), 6 mg HA (Group 2), 0.25 mg AOD9604 (Group 3), and 0.25 mg AOD9604 with 6 mg HA (Group 4) were administered for 4-7 weeks after the first intra-articular collagenase injection. The degree of cartilage degeneration was assessed using morphological and histopathological findings, and the degree of lameness was observed at 8 weeks after the first collagenase injection.

Results: Mean gross morphological and histopathological scores were significantly higher in Group 1 than in Groups 2, 3, and 4, and the scores were significantly lower in Group 4 than in Groups 2 and 3. The lameness period in Group 4 was significantly shorter than those in Groups 1, 2, and 3. The lameness period in Group 1 was significantly longer than those in Groups 2 and 3.

Conclusion: Intra-articular AOD9604 injections using ultrasound guidance enhanced cartilage regeneration, and combined AOD9604 and HA injections were more effective than HA or AOD9604 injections alone in the collagenase-induced knee OA rabbit model.

Keywords: AOD9604; Collagenase; HA; Knee; Osteoarthritis; Ultrasound.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Collagenases / toxicity
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hyaluronic Acid / administration & dosage*
  • Injections, Intra-Articular / methods
  • Male
  • Osteoarthritis / chemically induced
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / pathology
  • Peptide Fragments / administration & dosage*
  • Rabbits
  • Somatostatin / administration & dosage*
  • Time Factors

Substances

  • AOD 9604
  • Adjuvants, Immunologic
  • Anti-Inflammatory Agents
  • Peptide Fragments
  • Somatostatin
  • Hyaluronic Acid
  • Collagenases