Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor)
Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor)
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DOI：
10.1359/jbmr.040322
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发表时间：
2004-08-01
影响因子：
6.2
通讯作者：
Takigawa, M
中科院分区：
文献类型：
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作者：
Nishida, T;Kubota, S;Takigawa, M
CTGF/CCN2是一种肥大的软骨细胞特异性基因产物，在实验性骨关节炎和关节软骨全层缺损两种动物模型中具有修复关节软骨损伤的能力。结缔组织生长因子(CTGF)/CCN2是一种独特的生长因子，可在体外刺激关节软骨细胞的增殖和分化，而不是肥大。本研究的目的是探讨重组CTGF/CCN2(rCTGF/CCN2)在大鼠关节软骨损伤修复中的作用。材料和方法：采用单碘乙酸(MIA)诱导的大鼠实验性骨关节炎模型和大鼠关节软骨全层损伤模型，观察重组CTGF/CCN2(rCTGF/CCN2)对损伤软骨修复的影响。结果：在MIA诱导的大鼠关节软骨损伤模型中，实时定量RT-PCR检测显示CTGF/CCN2的表达显著增加，免疫组织化学和原位杂交分析显示，聚集的软骨细胞产生了CTGF/CCN2。因此，CTGF/CCN2被认为在软骨修复中起关键作用。事实上，一次将rCTGF/CCN2明胶水凝胶(rCTGF/CCN2水凝胶)注射到MIA诱导的OA模型大鼠的关节腔内，可以修复其关节软骨，使其在组织学上与正常关节软骨相似。接下来，为了探讨rCTGF/CCN2在关节软骨修复中的作用，我们在关节软骨表面造成直径为2 mm的原位缺损，并将rCTGF/CCN2-水凝胶或PBS-水凝胶与胶原海绵一起植入其中。RCTGF/CCN2-水凝胶胶原组术后4周新生软骨充填。相反，当植入PBS水凝胶胶原时，只有软组织修复。与体内实验结果一致，rCTGF/CCN2可促进小鼠骨髓基质细胞II型胶原和aggrecan基因的表达，并在体外诱导软骨形成。结论：CTGF/CCN2在关节软骨再生中具有一定的应用价值。
CTGF/CCN2, a hypertrophic chondrocyte-specific gene product, possessed the ability to repair damaged articular cartilage in two animal models, which were experimental osteoarthritis and full-thickness defects of articular cartilage. These findings suggest that CTGF/CCN2 may be useful in regeneration of articular cartilage.Introduction: Connective tissue growth factor (CTGF)/CCN2 is a unique growth factor that stimulates the proliferation and differentiation, but not hypertrophy, of articular chondrocytes in vitro. The objective of this study was to investigate the therapeutic use of CTGF/CCN2.Materials and Methods: The effects of recombinant CTGF/CCN2 (rCTGF/CCN2) on repair of damaged cartilage were evaluated by using both the monoiodoacetic acid (MIA)-induced experimental rat osteoarthritis (OA) model and full-thickness defects of rat articular cartilage in vivo.Results: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which Clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2. Therefore, CTGF/CCN2 was suspected to play critical roles in cartilage repair. In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage. Next, to examine the effect of rCTGF/CCN2 on the repair of articular cartilage, we created defects (2 mm in diameter) on the surface of articular cartilage in situ and implanted rCTGF/CCN2-hydrogel or PBS-hydrogel therein with collagen sponge. In the group implanted with rCTGF/CCN2-hydrogel collagen, new cartilage filled the defect 4 weeks postoperatively. In contrast, only soft tissue repair occurred when the PBS-hydrogel collagen was implanted. Consistent with these in vivo effects, rCTGF/CCN2 enhanced type II collagen and aggrecan mRNA expression in mouse bone marrow-derived stromal cells and induced chondrogenesis in vitro.Conclusion: These findings suggest the utility of CTGF/CCN2 in the regeneration of articular cartilage.