CELL ORIGIN AND DIFFERENTIATION IN THE REPAIR OF FULL-THICKNESS DEFECTS OF ARTICULAR-CARTILAGE
CELL ORIGIN AND DIFFERENTIATION IN THE REPAIR OF FULL-THICKNESS DEFECTS OF ARTICULAR-CARTILAGE
复制标题
DOI：
10.2106/00004623-199304000-00009
复制
发表时间：
1993-04-01
影响因子：
5.3
通讯作者：
GLIMCHER, MJ
中科院分区：
文献类型：
--
作者：
SHAPIRO, F;KOIDE, S;GLIMCHER, MJ
本文对新西兰白色兔关节软骨直径为3毫米的圆柱形全层钻孔缺损修复过程中细胞的来源和分化进行了组织学研究。手术后允许动物自由活动。术后48周，对122只动物的364个个体缺损进行了检查。在最初的几天里，从表面边缘到表面边缘，在缺损处建立了血管弓，这有助于间充质细胞沿着长轴向内生长。如番红-O染色所定义的，软骨细胞外基质合成的第一个证据出现在第十天。两周后，几乎所有标本中的胶原组织表面下立即出现软骨，胶原组织富含扁平纤维软骨细胞。在三周时，几乎所有缺损部位都有一层界限分明的软骨层，其中含有软骨细胞。第六、八、十和十二周时，缺损基本上完全重新聚集，细胞逐渐分化为成软骨细胞、软骨细胞和成骨细胞，并在适当位置合成软骨和骨基质。24周时，潮标和致密板层软骨下骨板均已重建。 最初在缺损深处形成的松质编织骨被层状粗松质骨所取代，用H-3-胸苷和H-3-胞苷标记后的放射自显影表明，来自残余邻近关节软骨的软骨细胞不参与缺损的再增殖。骨髓间充质细胞的增殖和分化是其修复的主要途径。手术后7天关节内注射H-3-胸苷清楚地标记了这个间充质细胞池。最初由未分化的间充质细胞摄取的标记逐渐出现在成纤维细胞、成骨细胞、关节成软骨细胞和软骨细胞中，表明它们起源于骨髓的原始间充质细胞。在12至20周的许多缺损中观察到软骨基质退化的早期痕迹，在24、36、37、38、39四十八周。偏振光显微镜检查表明，新合成的修复基质未能粘附到紧邻钻孔的软骨上并与之整合，即使在光学显微镜检查显示组织明显连续的情况下。在许多情况下，修复和残留软骨之间存在明显的间隙。这种缺乏物理和化学键合的修复软骨和残余的相邻软骨的大分子成分之间可能允许微动和macromotion它们之间，这可能会引发软骨degeneration.Clinical相关性：知识的细胞生物学的关节软骨缺损的修复是必不可少的解释的结果，旨在改善修复的治疗干预措施。在没有任何特定治疗的情况下，许多家兔具有良好的组织学修复。我们建议通过使用统一尺寸和位置的缺陷来严格控制实验模型，以尽量减少响应的变化。修复评估应持续6至12个月，因为在此期间，大多数明显愈合良好的软骨发生失败。
The origin and differentiation of cells in the repair of three-millimeter-diameter, cylindrical, full-thickness drilled defects of articular cartilage were studied histologically in New Zealand White rabbits. The animals were allowed to move freely after the operation. Three hundred and sixty-four individual defects from 122 animals were examined as long as forty-eight weeks postoperatively. In the first few days, fibrinous arcades were established across the defect, from surface edge to surface edge, and this served to orient mesenchymal cell ingrowth along the long axes. The first evidence of synthesis of a cartilage extracellular matrix, as defined by safranin-O staining, appeared at ten days. At two weeks, cartilage was present immediately beneath the surface of collagenous tissue that was rich in flattened fibrocartilaginous cells in virtually all specimens. At three weeks, the sites of almost all of the defects had a well demarcated layer of cartilage containing chondrocytes. An essentially complete repopulation of the defects occurred at six, eight, ten, and twelve weeks, with progressive differentiation of cells to chondroblasts, chondrocytes, and osteoblasts and synthesis of cartilage and bone matrices in their appropriate locations. At twenty-four weeks, both the tidemark and the compact lamellar subchondral bone plate had been re-established. The cancellous woven bone that had formed initially in the depths of the defect was replaced by lamellar, coarse cancellous bone.Autoradiography after labeling with H-3-thymidine and H-3-cytidine demonstrated that chondrocytes from the residual adjacent articular cartilage did not participate in the repopulation of the defect. The repair was mediated wholly by the proliferation and differentiation of mesenchymal cells of the marrow. Intra-articular injections of H-3-thymidine seven days after the operation clearly labeled this mesenchymal cell pool. The label, initially taken up by undifferentiated mesenchymal cells, progressively appeared in fibroblasts, osteoblasts, articular chondroblasts, and chondrocytes, indicating their origin from the primitive mesenchymal cells of the marrow.Early traces of degeneration of the cartilage matrix were seen in many defects at twelve to twenty weeks, with the prevalence and intensity of the degeneration increasing at twenty-four, thirty-six, and forty-eight weeks. Polarized light microscopy demonstrated failure of the newly synthesized repair matrix to become adherent to, and integrated with, the cartilage immediately adjacent to the drill-hole, even when light microscopy had shown apparent continuity of the tissue. In many instances, a clear gap was seen between repair and residual cartilage. This lack of physical and chemical bonding between the macromolecular components of the repair cartilage and the residual adjacent cartilage may allow for micromotion and macromotion between them, which may initiate cartilage degeneration.CLINICAL RELEVANCE: Knowledge of the cell biology of the repair of defects in articular cartilage is essential for the interpretation of results of therapeutic interventions designed to improve repair. Many rabbits had excellent histological repair in the absence of any specific treatment. We recommend strict control of experimental models by use of defects of uniform size and location to minimize variations in response. Evaluation of repair should be continued for six to twelve months, as it is during this period that most failures of apparently well healed cartilage occur.