Mizuta Hiroshi, Kudo Satoshi, Nakamura Eiichi, Otsuka Yutaka, Takagi Katsumasa, Hiraki Yuji
Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Osteoarthritis Cartilage. 2004 Jul;12(7):586-96. doi: 10.1016/j.joca.2004.04.008.
In full-thickness articular defects, fibroblast growth factor-2 (FGF-2) participates in the chondrogenic repair response which occurs in a defect-size dependent manner. Here we demonstrate that FGF-2 plays a critical role in the proliferation of pre-chondrogenic mesenchymal cells during chondrogenic induction.
Three-millimeter- or 5-mm-diameter cylindrical defects were created in the femoral trochlea of the rabbit knee. The defects received sterile saline or FGF-2 (50 pg/h) via an osmotic pump for the initial 2 weeks. We assessed the proliferative capacity of undifferentiated mesenchymal cells in the reparative tissue with the anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody. Using a total of 180 rabbits, we performed three sets of experiments.
In the 3-mm-diameter defects, undifferentiated mesenchymal cells spontaneously initiated chondrogenic differentiation within 2 weeks, resulting in the regeneration of surfacing articular cartilage concomitantly with the repair of subchondral bone. No evidence of chondrogenesis was seen in the 5-mm-diameter defects, whereas application of FGF-2 promoted successful regeneration of articular cartilage. In the 3-mm-diameter defects and in the FGF-2-treated 5-mm defects, PCNA immunoreactivity was widely detected in undifferentiated cells in the reparative tissue at 1 and 2 weeks after creation of the defects. In contrast, in the 5-mm-diameter defects without FGF-2 treatment, the PCNA-positive cells were found at a significantly lower incidence.
Active expansion of undifferentiated cell population mediated by FGF-2 is required to initiate and support a chondrogenic repair response in full-thickness defects of articular cartilage. Endogenous FGF-2 could not meet the requirements of growth signaling in the center of larger sized defects.
在全层关节缺损中，成纤维细胞生长因子-2（FGF-2）参与以缺损大小依赖方式发生的软骨形成修复反应。在此我们证明FGF-2在软骨形成诱导过程中对软骨前间充质细胞的增殖起关键作用。
在兔膝关节股骨滑车处制造直径3毫米或5毫米的圆柱形缺损。缺损在最初2周通过渗透泵接受无菌盐水或FGF-2（50 pg/h）。我们用抗增殖细胞核抗原（PCNA）单克隆抗体评估修复组织中未分化间充质细胞的增殖能力。使用总共180只兔子，我们进行了三组实验。
在直径3毫米的缺损中，未分化间充质细胞在2周内自发启动软骨形成分化，导致表层关节软骨再生并伴有软骨下骨修复。在直径5毫米的缺损中未见软骨形成证据，而应用FGF-2促进了关节软骨的成功再生。在直径3毫米的缺损和FGF-2处理的5毫米缺损中，在缺损形成后1周和2周时，PCNA免疫反应性在修复组织的未分化细胞中广泛检测到。相比之下，在未用FGF-2处理的直径5毫米的缺损中，PCNA阳性细胞的发生率显著较低。
FGF-2介导的未分化细胞群体的活跃扩增是启动和支持关节软骨全层缺损中软骨形成修复反应所必需的。内源性FGF-2无法满足较大尺寸缺损中心生长信号的需求。
