A comparative dose-response study of cartilage-derived morphogenetic protein (CDMP)-1,-2 and-3 for tendon healing in rats

Cartilage-derived morphogenetic proteins (CDMPs), belonging to the bone morphogenetic protein (BMP) family, are known to be cartilage and bone inducers as well as to induce tendon and ligament-like tissue. In this study we investigated the influence of CDMP-1, -2 or -3 at four different doses (0, 0.4, 2 and 10 mug) on tendon healing in a rat model, as well as differences in osteogenesis between the different CDMPs and doses. In 110 rats, a 3 mm segment of the Achilles tendon was removed via a 2 mm skin incision. CDMP-1, -2 or -3 was injected into the defect 6 h postoperative. The rats were killed 8 days after operation. The tendon regenerates were tested biomechanically. There was a significant dose-related increase in strength and stiffness with all three CDMPs, but no difference between the CDMPs was found. Another 50 rats were used to compare the highest dose of the CDMPs with controls and osteogenic protein 1 (OP-1), as regards cartilage or bone formation after 4 weeks. Cartilage occurred in all groups, including the controls. Some specimens in all groups contained bone, except the controls. No difference between the CDMPs could be demonstrated. The CDMP-1, CDMP-3 and OP-1 groups contained significantly more calcium than controls. Only the CDMP-2 group and the controls contained significantly less calcium than the OP-1 group. In conclusion, the three CDMPs appeared similar as regards improvement of tendon repair and osteogenicity in this setting. (C) 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.