Drexel University, Philadelphia, Pennsylvania.
Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Arthritis Rheumatol. 2020 Aug;72(8):1266-1277. doi: 10.1002/art.41254. Epub 2020 Jul 8.
To elucidate the role of decorin, a small leucine-rich proteoglycan, in the degradation of cartilage matrix during the progression of post-traumatic osteoarthritis (OA).
Three-month-old decorin-null (Dcn ) and inducible decorin-knockout (Dcn ) mice were subjected to surgical destabilization of the medial meniscus (DMM) to induce post-traumatic OA. The OA phenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan (sGAG) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy-nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro-computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild-type and Dcn mice were stimulated with the inflammatory cytokine interleukin-1β (IL-1β) in vitro (n = 6 mice per group). The resulting chondrocyte response to IL-1β and release of sGAGs were quantified.
In both Dcn and Dcn mice, the absence of decorin resulted in accelerated sGAG loss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control (P < 0.05). Also, Dcn mice developed more salient osteophytes, illustrating more severe OA. In cartilage explants treated with IL-1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion of sGAGs was released to the media from Dcn mouse explants, in both live and devitalized conditions (P < 0.05).
In post-traumatic OA, decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration.
阐明小富含亮氨酸的蛋白聚糖decorin 在创伤后骨关节炎（OA）进展过程中软骨基质降解中的作用。
对 3 月龄的 decorin 缺失（Dcn ）和诱导型 decorin 敲除（Dcn ）小鼠进行内侧半月板（DMM）手术不稳定化以诱导创伤后 OA。通过组织学分析评估由此产生的 OA 表型（每组 6 只小鼠），通过扫描电子显微镜评估关节形态和硫酸化糖胺聚糖（sGAG）染色（每组 4 只小鼠），通过原子力显微镜-纳米压痕评估组织模量（每组 5 只或更多只小鼠），通过微计算机断层扫描评估软骨下骨结构（每组 5 只小鼠）。从野生型和 Dcn 小鼠的股骨头软骨中取出软骨外植体，在体外用炎性细胞因子白细胞介素-1β（IL-1β）刺激（每组 6 只小鼠）。定量分析软骨细胞对 IL-1β的反应和 sGAG 的释放。
在 Dcn 和 Dcn 小鼠中，缺乏 decorin 导致 sGAG 丢失加速，并且与对照相比，软骨表面形成高度排列的胶原纤维（P < 0.05）。此外，Dcn 小鼠形成了更明显的骨赘，表明 OA 更严重。在经 IL-1β处理的软骨外植体中，decorin 的缺失并未改变合成代谢或分解代谢基因的表达。然而，在有活力和无活力条件下，Dcn 小鼠外植体释放到培养基中的 sGAG 比例更大（P < 0.05）。
在创伤后 OA 中，decorin 延迟了碎片化聚集蛋白聚糖的丢失和软骨表面的纤维化，从而在改善软骨退变方面发挥了保护作用。
