Orthopaedics Research Laboratory, Lady Davis Institute for Medical Research - Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC, H3T 1E2, Canada.
Department of Surgery, McGill University, 3655 Promenade Sir William Osler, Montréal, QC, H3G 1Y6, Canada.
Arthritis Res Ther. 2018 Aug 29;20(1):201. doi: 10.1186/s13075-018-1625-9.
The degeneration of the intervertebral disc (IVD) is characterized by proteolytic degradation of the extracellular matrix, and its repair requires the production of an extracellular matrix with a high proteoglycan-to-collagen ratio characteristic of a nucleus pulposus (NP)-like phenotype in vivo. At the moment, there is no medical treatment to reverse or even retard disc degeneration. The purpose of the present study was to determine if a low dose of short link N (sLN), a recently discovered fragment of the link N peptide, could behave in a manner similar to that of link N in restoring the proteoglycan content and proteoglycan-to-collagen ratio of the disc in a rabbit model of IVD degeneration, as an indication of its potential therapeutic benefit in reversing disc degeneration.
Adolescent New Zealand white rabbits received an annular puncture with an 18-gauge needle into two noncontiguous discs to induce disc degeneration. Two weeks later, either saline (10 μL) or sLN (25 μg in 10 μL saline) was injected into the center of the NP. The sLN concentration was empirically chosen at a lower molar concentration equivalent to half that of link N (100 μg in 10 μL). The effect on radiographic, biochemical and histologic changes were evaluated.
Following needle puncture, disc height decreased by about 25-30% within 2 weeks and maintained this loss for the duration of the 12-week study; a single 25-μg sLN injection at 2 weeks partially restored this loss in disc height. sLN injection led to an increase in glycosaminoglycans (GAG) content 12 weeks post-injection in both the NP and annulus fibrosus (AF). There was a trend towards maintaining control disc collagen-content with sLN supplementation and the GAG-to-collagen ratio in the NP was increased when compared to the saline group.
When administered to the degenerative disc in vivo, sLN injection leads to an increase in proteoglycan content and a trend towards maintaining control disc collagen content in both the NP and AF. This is similar to link N when it is administered to the degenerative disc. Thus, pharmacologically, sLN supplementation could be a novel therapeutic approach for treating disc degeneration.
椎间盘（IVD）的退变特征为细胞外基质的蛋白水解降解，其修复需要产生具有核髓样表型的细胞外基质，其特征是糖胺聚糖与胶原蛋白的比例高。目前，尚无医学治疗方法可以逆转甚至延缓椎间盘退变。本研究旨在确定低剂量短链接 N（sLN），一种新发现的链接 N 肽片段，是否可以像链接 N 一样恢复兔椎间盘退变模型中椎间盘的糖胺聚糖含量和糖胺聚糖与胶原蛋白的比例，作为其逆转椎间盘退变的潜在治疗益处的指标。
青少年新西兰白兔接受 18 号针的环形穿刺，将两个非连续的椎间盘穿刺，以诱导椎间盘退变。2 周后，将盐水（10 μL）或 sLN（10 μL 盐水中的 25 μg）注入 NP 中心。根据经验选择 sLN 浓度，使其摩尔浓度相当于链接 N 的一半（10 μL 中的 100 μg）。评估对影像学、生化和组织学变化的影响。
在针刺后 2 周内，椎间盘高度下降约 25-30%，并在 12 周研究期间保持这种损失；在 2 周时单次注射 25 μg sLN 可部分恢复这种椎间盘高度的损失。sLN 注射导致注射后 12 周 NP 和纤维环（AF）中的糖胺聚糖（GAG）含量增加。与盐水组相比，sLN 补充剂可维持控制盘胶原蛋白含量的趋势，NP 中的 GAG 与胶原蛋白的比例增加。
当体内注射到退变的椎间盘时，sLN 注射可增加糖胺聚糖含量，并趋向于维持 NP 和 AF 中控制盘的胶原蛋白含量。这与链接 N 给药于退变的椎间盘时相似。因此，药理学上，sLN 补充剂可能是治疗椎间盘退变的一种新的治疗方法。
