Clinical Research Center, National Hospital Organization Sagamihara Hospital, 18-1 Sakuradai, Sagamihara, Kanagawa, 252-0315, Japan.
Department of Orthopaedic Surgery, Tokyo Yamate Medical Center, 3-22-1 Hyakuninncyou, Shinjyuku-ku, Tokyo, 169-0073, Japan.
BMC Musculoskelet Disord. 2019 May 18;20(1):232. doi: 10.1186/s12891-019-2596-y.
In osteoarthritis (OA), cartilage matrix is lost despite vigorous chondrocyte anabolism. In this study, we attempted to determine whether altered matrix synthesis is involved in this paradox in disease progression through gene expression analysis and ultrastructural analysis of collagen fibrils within the cartilage matrix.
Cartilage tissues were obtained from 29 end-stage OA knees and 11 control knees. First, cDNA microarray analysis was performed and the expression of 9 genes involved in collagen fibrillogenesis was compared between OA and control cartilages. Then their expression was investigated in further detail by a quantitative polymerase chain reaction (qPCR) analysis combined with laser capture microdissection. Finally, collagen fibril formation was compared between OA and control cartilage by transmission electron microscopy.
The result of the microarray analysis suggested that the expression of type IX and type XI collagens and fibrillogenesis-related small leucine-rich proteoglycans (SLRPs) may be reduced in OA cartilage relative to the type II collagen expression. The qPCR analysis confirmed these results and further indicated that the relative reduction in the minor collagen and SLRP expression may be more obvious in degenerated areas of OA cartilage. An ultrastructural analysis suggested that thicker collagen fibrils may be formed by OA chondrocytes possibly through reduction in the minor collagen and SLRP expression.
This may be the first study to report the possibility of altered collagen fibrillogenesis in OA cartilage. Disturbance in collagen fibril formation may be a previously unidentified mechanism underlying the loss of cartilage matrix in OA.
在骨关节炎(OA)中,尽管软骨细胞有旺盛的合成代谢,但软骨基质仍会丢失。在这项研究中,我们试图通过基因表达分析和软骨基质内胶原纤维的超微结构分析,确定在疾病进展过程中基质合成的改变是否与这一矛盾有关。
从 29 个终末期 OA 膝关节和 11 个对照膝关节中获取软骨组织。首先,进行 cDNA 微阵列分析,比较 OA 和对照软骨中 9 个参与胶原纤维形成的基因的表达。然后,通过定量聚合酶链反应(qPCR)分析结合激光捕获显微切割,进一步详细研究其表达。最后,通过透射电子显微镜比较 OA 和对照软骨中的胶原纤维形成。
微阵列分析的结果表明,与 II 型胶原表达相比,OA 软骨中 IX 型和 XI 型胶原以及纤维形成相关的小富含亮氨酸的蛋白聚糖(SLRPs)的表达可能降低。qPCR 分析证实了这些结果,并进一步表明,OA 软骨退变区中,次要胶原和 SLRP 表达的相对减少可能更为明显。超微结构分析表明,OA 软骨细胞可能通过降低次要胶原和 SLRP 的表达来形成更厚的胶原纤维。
这可能是第一项报道 OA 软骨中胶原纤维形成改变的可能性的研究。胶原纤维形成的紊乱可能是 OA 中软骨基质丢失的一个以前未被识别的机制。