Biomedical Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK.
Department of Orthopaedics and Trauma, Royal Infirmary of Edinburgh, Edinburgh, UK.
J Cell Physiol. 2021 Nov;236(11):7672-7681. doi: 10.1002/jcp.30418. Epub 2021 May 26.
Chondrocytes with abnormal morphology are present in nondegenerate human cartilage suggesting dedifferentiation to a fibroblastic phenotype and production of a mechanically-weakened matrix of unknown composition. We determined the relationship between in situ chondrocyte morphology, chondrocyte clusters, and levels of cell-associated collagen type I. Chondrocyte morphology in fresh femoral head cartilage from 19 patients with femoral neck fracture and collagen type I labelling was identified with Cell Tracker fluorescence and immunofluorescence, respectively, in axial/coronal orientations using confocal microscopy with images analysed by Imaris . In axial images of grade 0 cartilage, 87 ± 8% were normal chondrocytes with a small (10 ± 6%) abnormal population possessing ≥1 cytoplasmic process. More normal chondrocytes (78 ± 11%) were collagen type I negative than those labelling positively (p < 0.001). For abnormal chondrocytes, 81 ± 14% labelled negatively for collagen type I compared to those labelling positively (19 ± 3%; p = 0.007; N(n)=11(3)). Overall, approximately 9% of the cells in normal cartilage labelled for collagen type I. With degeneration, the percentage of normal chondrocytes decreased (p < 0.001) but increased for abnormal cells (p = 0.036) and clusters (p = 0.003). A larger percentage of normal, abnormal and clustered chondrocytes now demonstrated collagen type I labelling (p = 0.004; p = 0.009; p = 0.001 respectively). Coronal images exhibited increased (p = 0.001) collagen type I labelling in the superficial zone of mildly degenerate cartilage with none in the mid or deep zones. These results show that collagen type I was identified around normal and abnormal chondrocytes in nondegenerate cartilage, which increased with degeneration. This suggested the presence of mechanically weak fibro-cartilaginous repair tissue in otherwise macroscopically nondegenerate human cartilage which progressed with degeneration as occurs in osteoarthritis.
软骨细胞形态异常存在于非退变的人类软骨中,提示软骨细胞去分化为成纤维细胞表型,并产生组成未知的机械弱化基质。我们确定了原位软骨细胞形态、软骨细胞簇和细胞相关胶原 I 水平之间的关系。使用共聚焦显微镜,以轴向/冠状方向分别用 Cell Tracker 荧光和免疫荧光标记新鲜股骨头软骨中的软骨细胞形态和胶原 I 标记,并用 Imaris 分析图像。在 0 级软骨的轴向图像中,87±8%的软骨细胞形态正常,只有 10±6%的异常细胞具有至少 1 个细胞质突起。与胶原 I 阳性标记的软骨细胞相比,胶原 I 阴性标记的正常软骨细胞更多(p<0.001)。对于异常软骨细胞,81±14%的细胞胶原 I 阴性标记,而阳性标记的细胞为 19±3%(p=0.007;N(n)=11(3))。总的来说,大约 9%的正常软骨细胞胶原 I 阳性标记。随着退变,正常软骨细胞的百分比减少(p<0.001),但异常细胞(p=0.036)和细胞簇(p=0.003)的百分比增加。现在,更多的正常、异常和簇集的软骨细胞显示胶原 I 标记(p=0.004;p=0.009;p=0.001)。冠状图像显示轻度退变软骨的浅层区胶原 I 标记增加(p=0.001),中层和深层区则没有。这些结果表明,在非退变软骨中,胶原 I 围绕正常和异常软骨细胞被识别,并且随着退变而增加。这表明在其他宏观上非退变的人类软骨中存在机械弱化的纤维软骨修复组织,这种情况随着骨关节炎的发生而进展。