title: Effects of local application of growth and differentiation factor-5 (GDF-5) in a full-thickness cartilage defect model.
abstract: 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.
authors.affiliation: Orthopädische Universitätsklinik Heidelberg, Heidelberg, Germany. hans-georg.simank@ok.uni-heidelberg.de
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Simank
authors.forename: Consolato
authors.initials: C
authors.lastname: Sergi
authors.forename: Martin
authors.initials: M
authors.lastname: Jung
authors.forename: Stefanie
authors.initials: S
authors.lastname: Adolf
authors.forename: Christina
authors.initials: C
authors.lastname: Eckhardt
authors.forename: Volker
authors.initials: V
authors.lastname: Ehemann
authors.forename: Rainer
authors.initials: R
authors.lastname: Ries
authors.forename: Christoph
authors.initials: C
authors.lastname: Lill
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Richter
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000627:therapeutic use*; D001861:Bone Regeneration; D002358:Cartilage, Articular / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005333:Fetus; D005434:Flow Cytometry; D055428:Growth Differentiation Factor 5; D010006:Osteoblasts / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D012886:Skull / Q000166:cytology; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D055428:Growth Differentiation Factor 5; D011994:Recombinant Proteins