Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
Inflammation and Cartilage Cellular Research Group, IMIM (Hospital del Mar Medical Research Institute) Rheumatology Department, Parc de Salut Mar, Hospital del Mar, Barcelona, Spain.
Sci Rep. 2018 Jan 11;8(1):457. doi: 10.1038/s41598-017-18047-w.
The SLRP opticin (OPTC) has been demonstrated to be produced and degraded in osteoarthritic (OA) human cartilage. Here, we investigated the in vivo effect of OPTC deficiency in OA cartilage. OA was induced in 10-week-old Optc and Optc mice. Ten weeks post-surgery, cartilage was processed for histology and immunohistochemistry. SLRP expression was determined in non-operated mouse cartilage. OA Optc demonstrated significant protection against cartilage degradation. Data revealed that in non-operated Optc cartilage, expression of SLRPs lumican and epiphycan was up-regulated at day 3 and in 10-week-olds (p ≤ 0.039), and fibromodulin down-regulated in 10-week-olds (p = 0.001). Immunohistochemistry of OA mice showed a similar pattern. In OA Optc cartilage, markers of degradation and complement factors were all down-regulated (p ≤ 0.038). In OA Optc cartilage, collagen fibers were thinner and better organized (p = 0.038) than in OA Optc cartilage. The protective effect of OPTC deficiency during OA results from an overexpression of lumican and epiphycan, known to bind and protect collagen fibers, and a decrease in fibromodulin, contributing to a reduction in the complement activation/inflammatory process. This work suggests that the evaluation of the composition of the different SLRPs in OA cartilage could be applied as a new tool for OA prognosis classification.
SLRP 核心蛋白聚糖（OPTC）已被证明在骨关节炎（OA）人类软骨中产生和降解。在这里，我们研究了 OPTC 缺乏对 OA 软骨的体内影响。在 10 周龄的 Optc 和 Optc 小鼠中诱导 OA。手术后 10 周，对软骨进行组织学和免疫组织化学处理。测定了非手术小鼠软骨中的 SLRP 表达。OA Optc 对软骨降解有显著的保护作用。数据显示，在非手术 Optc 软骨中，SLRPs 核心蛋白聚糖和软骨寡聚基质蛋白的表达在第 3 天和 10 周龄时上调（p≤0.039），而纤维连接蛋白在 10 周龄时下调（p=0.001）。OA 小鼠的免疫组织化学显示出类似的模式。在 OA Optc 软骨中，降解标志物和补体因子均下调（p≤0.038）。在 OA Optc 软骨中，胶原纤维更细，排列更有序（p=0.038），与 OA Optc 软骨相比。OPTC 缺乏在 OA 中的保护作用是由于核心蛋白聚糖和软骨寡聚基质蛋白的过度表达，已知它们可以结合和保护胶原纤维，以及纤维连接蛋白的减少，有助于减少补体激活/炎症过程。这项工作表明，对 OA 软骨中不同 SLRPs 组成的评估可以作为 OA 预后分类的新工具。
