Analyses of early events during chondrogenic repair in rat full-thickness articular cartilage defects
Analyses of early events during chondrogenic repair in rat full-thickness articular cartilage defects
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DOI：
10.1007/s00774-009-0038-x
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发表时间：
2009-05-01
影响因子：
3.3
通讯作者：
Hiraki, Yuji
中科院分区：
文献类型：
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作者：
Anraku, Yoshihisa;Mizuta, Hiroshi;Hiraki, Yuji
在这项研究中，我们研究了关节软骨全层缺损修复过程中软骨分化开始期间发生的细胞事件。使用定制的双刀片装置在大鼠股骨髌骨沟中制造 V 形全层软骨缺损（宽度 0.7 或 1.5 毫米；深度 0.8 毫米；长度 4 毫米）。使用半定量组织学分级量表检查这些软骨缺陷修复反应的时间过程。在较大的 1.5 毫米缺损中，软骨修复反应未能发生，该缺损仅被纤维疤痕组织覆盖。相比之下，在 0.7 毫米宽的较小缺损中，4 周后，透明样关节软骨随着软骨下骨的修复而再生。然后通过免疫组织化学和原位杂交对修复区域的细胞进行表征。未分化的间充质细胞在产生后 4 天内迁移到缺损处并填充空腔。 PCNA、N-钙粘蛋白和 PTH/PTHrP 受体的表达在缺损中心的细胞中被诱导，其中 II 型胶原蛋白阳性的多边形细胞也在第 7 天开始出现。骨髓源性间充质细胞在初始迁移和填充较小的 0.7 毫米缺损后，在诱导的软骨空腔中获得更高水平的增殖活性。在大鼠关节软骨的再生修复过程中，有一个独特的步骤，似乎类似于软骨形成过程中关键的软骨前凝结。
In this study we investigated the cellular events that occur during the onset of chondrogenic differentiation during the repair of full-thickness defects of articular cartilage. The V-shaped full-thickness cartilage defects (width 0.7 or 1.5 mm; depth 0.8 mm; length 4 mm) were created in the femoral patellar groove of rats using a custom-built twin-blade device. The time course of the repair response in these cartilage defects was examined using a semi-quantitative histological grading scale. Cartilaginous repair responses failed to occur in the larger 1.5 mm defects, which was covered only by fibrous scar tissue. In contrast, hyaline-like articular cartilage was regenerated concomitantly with the repair of the subchondral bone by 4 weeks in smaller 0.7 mm width defects. Cells in the reparative regions were then characterized by immunohistochemistry and in situ hybridization. Undifferentiated mesenchymal cells migrate into the defects and fill the cavities within 4 days of their creation. The expression of PCNA, N-cadherin, and PTH/PTHrP receptors was induced in cells at the center of the defects, where type II collagen-positive polygonal-shaped cells also begin to appear at day 7. Marrow-derived mesenchymal cells acquire higher levels of proliferative activity in induced cartilage cavities after their initial migration and filling of the smaller 0.7 mm defects. During the regenerative repair of articular cartilage in the rat, there is a distinctive step that appears to be analogous to the precartilaginous condensation that is pivotal during chondrogenesis in development.