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.

Growth differentiation factors (GDFs) regulate homeostasis by amplifying extracellular matrix anabolism and inhibiting pro-inflammatory cytokine production in the intervertebral disc (IVD). The aim of this study was to elucidate the effects of GDF-6 on human IVD nucleus pulposus (NP) cells using a three-dimensional culturing system in vitro and on rat tail IVD tissues using a puncture model in vivo. In vitro, Western blotting showed decreased GDF-6 expression with age and degeneration severity in surgically collected human IVD tissues (n = 12). Then, in moderately degenerated human IVD NP cells treated with GDF-6 (100 ng/mL), immunofluorescence demonstrated an increased expression of matrix components including aggrecan and type II collagen. Quantitative polymerase chain reaction analysis also presented GDF-6-induced downregulation of pro-inflammatory tumor necrosis factor (TNF)-α (p = 0.014) and interleukin (IL)-6 (p = 0.016) gene expression stimulated by IL-1β (10 ng/mL). Furthermore, in the mitogen-activated protein kinase pathway, Western blotting displayed GDF-6-induced suppression of p38 phosphorylation (p = 0.041) under IL-1β stimulation. In vivo, intradiscal co-administration of GDF-6 and atelocollagen was effective in alleviating rat tail IVD annular puncture-induced radiologic height loss (p = 0.005), histomorphological degeneration (p < 0.001), matrix metabolism (aggrecan, p < 0.001; type II collagen, p = 0.001), and pro-inflammatory cytokine production (TNF-α, p < 0.001; IL-6, p < 0.001). Consequently, GDF-6 could be a therapeutic growth factor for degenerative IVD disease.

Background and Objectives: The impact of the duration of symptoms (DOS) on postoperative clinical outcomes of patients with degenerative lumbar spinal diseases is important for determining the optimal timing of surgical intervention; however, the timing remains controversial. This prospective case–control study aimed to investigate the influence of the preoperative DOS on surgical outcomes in minimally invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF). Materials and Methods: Patients who underwent single-level TLIF for lumbar degenerative diseases between 2017 and 2018 were reviewed. Only patients with full clinical data during the 1-year follow-up period were included. The patients were divided into two groups (DOS < 12 months, group S; DOS ≥ 12 months, group L). The clinical outcomes, including the Oswestry disability index (ODI) and visual analog scale (VAS) for lower back pain, leg pain, and numbness, were investigated preoperatively and at 1, 3, and 6 months, as well as 1 year, after surgery. Furthermore, postoperative patient satisfaction 1 year after surgery was also surveyed. Results: A total of 163 patients were assessed: 60 in group S and 103 in group L. No differences in baseline characteristics and clinical outcomes were found. The ODI and VAS significantly improved from the baseline to each follow-up period (all p < 0.01). Group S had significantly lower ODI scores at 3 months (p = 0.019) and 6 months (p = 0.022). In addition, group S had significantly lower VAS scores for leg pain at 3 months (p = 0.027). In a comparison between both groups, only the patients with cauda equina symptoms showed that ODI and leg pain VAS scores at 3 months after surgery were significantly lower in group S (19.9 ± 9.1 vs. 14.1 ± 12.5; p = 0.037, 7.4 ± 13.9 vs. 14.7 ± 23.1; p = 0.032, respectively). However, the clinical outcomes were not significantly different between both groups 1 year after surgery. Patient satisfaction was also not significantly different between both groups. Conclusions: Patients with a shorter DOS tended to have a significantly slower recovery; however, clinical outcomes 1 year after surgery were good, regardless of the DOS.