Requirement of fibroblast growth factor signaling for regeneration of epiphyseal morphology in rabbit full-thickness defects of articular cartilage.
The involvement of fibroblast growth factor-2 (FGF-2) during the repair process in rabbit full-thickness defects of articular cartilage was studied. Fibroblast growth factor-2 (50 pg/h) was administered for 2 weeks in a 5 mm defect of articular cartilage, which is large enough not to repair spontaneously. The administration of FGF-2 resulted in the regeneration of the articular cartilage and the subchondral bone within 8 weeks. In these defects, undifferentiated mesenchymal cells initiated chondrogenic differentiation coupled with replacement by subchondral bone, resulting in the resurfacing of the defects with hyaline cartilage and the recovery of subchondral bone up to the original bone-articular cartilage junction. In rabbits, full-thickness defects are capable of regenerating articular cartilage as long as the defect size is limited to < or = 3 mm in diameter. In the defects, strong immunoreactivity for FGF-2 was observed in the granulation tissue filling the defects in the early stage of repair, in association with the expression of FGF-2 mRNA shown by in situ hybridization. Once the undifferentiated mesenchymal cells had differentiated into chondrocytes, both the immunoreactivity and the in situ hybridization signal declined significantly. Upon the local administration of a monoclonal antibody against FGF-2 (bFM-1, 50 ng/h), the defects were filled with fibrous tissue and no resurfacing hyaline cartilage was formed. Compared to the non-treated defects, there were marked increases in FGF-2 immunoreactivity and the overexpression of FGF-2 mRNA in the reparative tissue in the bFM-1-treated defects. This rebound phenomenon indicates that the autocrine FGF-2 signaling is critically important for the regeneration of articular cartilage.
Otsuka
Y
Y
Department of Orthopaedic Surgery, Kumamoto University School of Medicine, Japan.
Mizuta
H
H
Takagi
K
K
Iyama
K
K
Yoshitake
Y
Y
Nishikawa
K
K
Suzuki
F
F
Hiraki
Y
Y
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000276:immunology / Q000502:physiology*; D006132:Growth Plate / Q000166:cytology / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D011817:Rabbits; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016222:Fibroblast Growth Factor 2