In a rabbit knee‑arthritis model, injecting the peptide AOD9604 directly into the joint helped the cartilage heal, and the benefit was even bigger when it was mixed with hyaluronic acid. The combo also made the rabbits limp for a shorter time than any single treatment or placebo.

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