title: Thrombospondin-1 prevents excessive ossification in cartilage repair tissue induced by osteogenic protein-1.
abstract: This study investigated the effect of thrombospondin-1 (TSP-1) on the formation of cartilage repair tissue in combination with stimulation by osteogenic protein-1 (OP-1). In miniature pigs, articular cartilage lesions in the femoral trochlea were treated by the microfracture technique and either received no further treatment (MFX), or were treated by additional application of recombinant osteogenic protein-1 (MFX+OP-1), recombinant TSP-1 (MFX+TSP-1), or a combination of both proteins (MFX+TSP-1+OP-1). Six and 26 weeks after surgery, the repair tissue and the degree of endochondral ossification were assessed by histochemical and immunohistochemical methods detecting collagen types I, II, X, TSP-1, and CD31. Microfracture treatment merely induced the formation of inferior fibrocartilaginous repair tissue. OP-1 stimulated chondrogenesis, but also induced chondrocyte hypertrophy, characterized by synthesis of collagen type X, and excessive bone formation. Application of TSP-1 inhibited inadvertant endochondral ossification, but failed to induce chondrogenesis. In contrast, the simultaneous application of both TSP-1 and OP-1 induced and maintained a permanent, nonhypertrophic chondrocyte-like phenotype within cartilage repair tissue. The data of this study demonstrate that OP-1 and TSP-1 complement each other in a functional manner. While OP-1 induces chondrogenesis of the ingrowing cells, TSP-1 prevents their further hypertrophic differentiation and prevents excessive endochondral ossification within the lesions.
authors.affiliation: Department of Orthopaedic Trauma Surgery, University Hospital Erlangen, Erlangen, Germany. kolja.gelse@web.de
authors.forename: Kolja
authors.initials: K
authors.lastname: Gelse
authors.forename: Patricia
authors.initials: P
authors.lastname: Klinger
authors.forename: Matthias
authors.initials: M
authors.lastname: Koch
authors.forename: Cordula
authors.initials: C
authors.lastname: Surmann-Schmitt
authors.forename: Klaus
authors.initials: K
authors.lastname: von der Mark
authors.forename: Bernd
authors.initials: B
authors.lastname: Swoboda
authors.forename: Friedrich F
authors.initials: FF
authors.lastname: Hennig
authors.forename: Johannes
authors.initials: J
authors.lastname: Gusinde
mesh_terms: D000818:Animals; D054544:Arthroplasty, Subchondral; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D002357:Cartilage Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D020219:Chondrogenesis / Q000187:drug effects; D003131:Combined Modality Therapy; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D006984:Hypertrophy; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D013314:Stress, Mechanical; D013552:Swine; D013556:Swine, Miniature; D019700:Thrombospondin 1 / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D055419:Bone Morphogenetic Protein 7; D019700:Thrombospondin 1