Requirement of fibroblast growth factor signaling for regeneration of epiphyseal morphology in rabbit full‐thickness defects of articular cartilage

Abstract

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.

The effect of fibroblast growth factor-2 on autologous osteochondral transplantation

“…These findings are consistent with the idea that the articular cartilage and subchondral bone were regenerated by FGF-2 [17]. Thus, the histological findings are compatible with those of the mechanical analysis, indicating that the grafts transplanted with FGF-2 hydrogel were more stable than those in the control group.…”

“…Weisser et al [27] reported that the treatment of chondrocyte cultures with FGF-2 had a stabilising effect on the differentiated state of the cells in vitro. Otsuka et al [17] reported that the articular cartilage Fig. 3a-c Histological evaluation of the junction between the graft and the host (Group I: defect filled with gelatin hydrogel including FGF-2, Group II: defect filled with gelatin hydrogel only, Group III: defect in which neither hydrogel nor FGF was used).…”

“…Basic fibroblastic growth factor (FGF-2) promotes the repair response in fullthickness articular cartilage defects and bone formation [3,4,6,17,25]. As a carrier material system, the gelatinhydrogel-incorporated growth factor leads to regeneration for cell differentiation and proliferation [24].…”

Experimental study of influence of direct bisphosphonate administration on bone substitute

“…The shape of the bone defect was set at a diameter of 5.0 mm and depth of 6.0 mm, for which natural healing of cartilage is not expected, based on studies reported by Otsuka et al 17) and Reddi et al 18,19) . Regarding DDM, Urist et al demonstrated that organic substances account for about 20% of tooth dentin in weight; the principal component is type I collagen, similarly to bone, with a trace amount of bone morphogenetic protein (BMP) having osteoinduction ability 20) .…”

Chitosan-Based Hyaluronic Acid Hybrid Polymer Fibers as a Scaffold Biomaterial for Cartilage Tissue Engineering

“…Under general anesthesia using intravenous pentobarbital (0.05 mg/kg) followed by isoflurane in oxygen gas anesthesia, through a medial parapatellar arthrotomy, a full-thickness osteochondral defect 5 mm in diameter and 2 mm deep was made by an electric-powered drill on the patellar groove of the bilateral distal femur. Previous studies have shown that such defects fail to repair spontaneously [40,41]. The tissue-engineered constructs using each scaffold-cushion-type or cylinder-type scaffold-were press-fit implanted into the defects after an eight week-cultivation in both treatment groups.…”