Effects of Local Application of Growth and Differentiation Factor-5 (GDF-5) in a Full-thickness Cartilage Defect Model

• Published in: Growth factors (Chur, Switzerland) Vol. 22; no. 1; pp. 35 - 43
• Main Authors: Simank, Hans-Georg, Sergi, Consolato, Jung, Martin, Adolf, Stefanie, Eckhardt, Christina, Ehemann, Volker, Ries, Rainer, Lill, Christoph, Richter, Wiltrud
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.03.2004; Taylor & Francis
• Subjects: Animals; Biocompatible Materials - metabolism; Bone Morphogenetic Proteins - administration & dosage; Bone Morphogenetic Proteins - therapeutic use; Bone Regeneration; Cartilage repair; Cartilage, Articular - injuries; Cartilage, Articular - pathology; Cartilage, Articular - physiology; Cells, Cultured; Collagen Type I - metabolism; Disease Models, Animal; Extracellular Matrix - metabolism; Female; Fetus; Flow Cytometry; Flow-cytometric analysis; GDF-5; Growth Differentiation Factor 5; Osteoblasts - drug effects; Osteochondral defect; Rabbits; Rats; Recombinant Proteins - therapeutic use; Skull - cytology; Time Factors; Tomography, X-Ray Computed
• ISSN: 0897-7194; 1029-2292
• DOI: 10.1080/08977190310001645207

Our purpose in this study was to investigate the effects of growth and differentiation factor-5 (GDF-5) on cartilage and subchondral bone in a rabbit model harboring an osteochondral defect for a period of 6 months. Absorbable composites were implanted in adult rabbits (18 controls, 18 animals with collagen-I matrix, and 18 animals with matrix plus GDF-5). After 4, 8, or 24 weeks the specimens were studied by histology, microcomputed tomography (microCT) and flow-cytometric analysis (FACS). Implantation of GDF-5 resulted in an improved histological appearance. This was the result of significantly improved defect filling at 4 and 8 weeks. At 24 weeks, however, there was no difference between the groups. The histological examination disclosed a predominance of fibrocartilage, and remodeled subchondral bone was also observed. MicroCT documented normal bone density in all groups, excluding subchondral sclerosis. At 24 weeks, FACS analysis revealed high apoptotic activity in the GDF-5-treated group. As far as we are aware, this is the first report of the effects of GDF-5 in a full-thickness cartilage defect model. We assume that recombinant GDF-5 contained on the carrier is probably able to accelerate the regeneration of the osteochondral defect owing to its availability. However, control of the protein delivery may require further investigation.