Intervertebral disc degeneration (IVDD) is a main cause of low back pain, and inflammatory factors play key roles in its pathogenesis. Gremlin-1 (Grem1) was reported to induce an inflammatory response in other fields. This study aimed to investigate the mechanisms of Grem1 in the degenerative process of intervertebral discs. Dysregulated genes were determined by analyzing microarray profiles. The expression of Grem1 in 17 human disc samples (male:female = 9:8) and rat models (n = 5 each group) was measured by western blotting (WB), real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC). The regulatory effects of Grem1 on apoptosis were examined using siRNAs, flow cytometry, immunofluorescence (IF), and WB. The therapeutic effect was evaluated by locally injecting specific Grem1 siRNA into IVDD rats. The expression of Grem1 was significantly increased in human degenerative intervertebral discs; furthermore, the expression of Grem1 positively correlated with the level of intervertebral disc degeneration. Grem1 was significantly overexpressed in tumor necrosis factor (TNF)-α-induced degenerative NP cells. Apoptosis in degenerative NP cells transfected with siRNA targeting Grem1 was significantly lower than that in the control group. Specific Grem1 siRNA markedly repressed the development of IVDD in surgery-induced IVDD rats. These results indicated that the expression of Grem1 was positively correlated with the severity of intervertebral disc degeneration, and Grem1 siRNA could inhibit Grem1-induced apoptosis and extracellular matrix alterations by mediating the TGF-β/Smad signaling pathway. This study may provide a therapeutic strategy for alleviating inflammation-induced apoptosis associated with intervertebral disc degeneration.

Visfatin reportedly induces the expression of proinflammatory cytokines. Severe grades of intervertebral disc disease (IVDD) exhibit higher expression of visfatin than mild ones. However, the direct relationship between visfatin and IVDD remains to be elucidated. This study aimed to clarify whether stimulation of visfatin in IVDD is mediated by IL-6. To investigate the role of visfatin in IVDD, a rat model of anterior disc puncture was established by injecting visfatin or PBS using a 27gauge needle. Results revealed an obvious aggravation of the histological morphology of IVDD in the visfatin group. On treating human NP cellswith visfatin, the levels of collagenII and aggrecan decreased and those of matrix metallopeptidase 3 and IL-6 gradually increased. A rapid increase in ERK, JNK, and p38 phosphorylation was also noted after visfatin treatment. Compared to those treated with visfatin alone, NP cells pretreated with ERK1/2, JNK, and p38 inhibitors or siRNA targeting p38, ERK, and JNK exhibited a significant suppression of IL-6. Our data represent the first evidence that visfatin promotes IL-6 expression in NP cells via the JNK/ERK/p38-MAPK signalling pathways. Further, our findings suggest epidural fat and visfatin as potential therapeutic targets for controlling IVDD-associated inflammation.

BackgroundThis is a retrospective study to evaluate the efficacy of percutaneous short segment fixation (PSSF) with or without intermediate screws in Magerl A3 thoracolumbar (TL) fractures accompanied with low bone mineral density (BMD).Methods From January 2017 to December 2018, 30 patients diagnosed with Magerl A3 TL fractures having a BMD between 0.5/cm2 and 1g/cm2 in the lumbar vertebrae with intact neurological functions and a history of major trauma who underwent PSSF with or without intermediate screws were enrolled in this study. The patients were divided into two groups of those with intermediate screws (group F) or without (group S). The operation time and intra-operation blood loss were recorded. Oswestry disability index (ODI) questionnaire and visual analogue scale (VAS) were employed as clinical assessments and quantified. Radiographic follow-up assessed according to the Cobb angle (CA), Vertebral wedge angle (VWA), and anterior vertebral body height (AVBH).ResultsLoose screws were observed in 4 of the 30 enrolled patients. Significant differences were observed in operation time and intra-operative blood loss between the two groups. The enrolled patients’ clinical results (VAS and ODI scores) were good, however, no significant differences during all follow-up periods were present between the two groups. Radiographic evaluation (CA, VWA and AVBH) improved immediately after surgery, but significant correction loss was observed in the follow-up periods, especially in the first month. Radiographic evaluation demonstrated no significant differences between the two groups.Conclusion Although the patients’ clinical results were satisfactory, PSSF could not resist the correction loss in Magerl A3 TL fractures accompanied with BMD below 1g/cm2. Accordingly, the use of intermediate pedicle screws may be unnecessary due to their limited ability in resisting correction loss and increasing operation time as well as intra-operation blood loss.