Otsuka Y, Mizuta H, Takagi K, Iyama K, Yoshitake Y, Nishikawa K, Suzuki F, Hiraki Y
Department of Orthopaedic Surgery, Kumamoto University School of Medicine, Japan.
Dev Growth Differ. 1997 Apr;39(2):143-56. doi: 10.1046/j.1440-169x.1997.t01-1-00003.x.
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.
研究了成纤维细胞生长因子-2（FGF-2）在兔关节软骨全层缺损修复过程中的作用。在直径5mm的关节软骨缺损处给予成纤维细胞生长因子-2（50 pg/h），该缺损面积较大，无法自发修复。给予FGF-2后，8周内关节软骨和软骨下骨实现再生。在这些缺损中，未分化的间充质细胞开始软骨形成分化，并伴有软骨下骨的替代，导致缺损表面被透明软骨覆盖，软骨下骨恢复至原始骨-关节软骨交界处。在兔中，只要缺损直径限制在≤3mm，全层缺损就能够再生关节软骨。在缺损处，修复早期填充缺损的肉芽组织中观察到FGF-2的强免疫反应性，同时原位杂交显示有FGF-2 mRNA表达。一旦未分化的间充质细胞分化为软骨细胞，免疫反应性和原位杂交信号均显著下降。局部给予抗FGF-2单克隆抗体（bFM-1，50 ng/h）后，缺损被纤维组织填充，未形成透明软骨表面覆盖。与未治疗的缺损相比，bFM-1治疗的缺损中修复组织的FGF-2免疫反应性和FGF-2 mRNA过表达明显增加。这种反弹现象表明，自分泌FGF-2信号对于关节软骨再生至关重要。
