Background: The leptin receptor-deficient knockout (db/db) mouse is a well-established model for studying type II diabetes mellitus (T2DM). T2DM is an important risk factor of intervertebral disc degeneration (IVDD). Although the relationship between type I diabetes and IVDD has been reported by many studies, few studies have reported the effects of T2DM on IVDD in db/db mice model. Methods: Mice were separated into 3 groups: wild-type (WT), db/db, and IGF-1 groups (leptin receptor-deficient mice were treated with insulin-like growth factor-1 (IGF-1). To observe the effects of T2DM and glucose-lowering treatment on IVDD, IGF-1 injection was used. The IVD phenotype was detected by H&E and safranin O fast green staining among db/db, WT and IGF-1 mice. The levels of blood glucose and weight in mice were also recorded. The changes in the mass of the trabecular bone in the fifth lumbar vertebra were documented by micro-computed tomography (micro-CT). Tunnel assays were used to detect cell apoptosis in each group. Results: The weight of the mice were 27.68 ± 1.6 g in WT group, which was less than 57.56 ± 4.8 g in db/db group, and 52.17 ± 3.7 g in IGF-1 injected group (P < 0.05). The blood glucose levels were also significantly higher in the db/db mice group. T2DM caused by leptin receptor knockout showed an association with significantly decreased vertebral bone mass and increased IVDD when compared to WT mice. The db/db mice induced by leptin deletion showed a higher percentage of MMP3 expression as well as cell apoptosis in IVDD mice than WT mice (P < 0.05), while IGF-1 treatment reversed this situation (P < 0.05). Conclusions: T2DM induced by leptin receptor knockout led to IVDD by increasing the levels of MMP3 and promoting cell apoptosis. IGF-1 treatment partially rescue the phenotype of IVDD induced by leptin receptor knockout.

Epidemiological studies have concluded that hyperlipidemia and atherosclerosis were related to intervertebral disc degeneration (IVDD). The presence of oxidized low density lipoprotein (ox-LDL) and the expression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) have not been explored in this tissue. In this study, we investigated the presence of ox-LDL and the expression of its receptor LOX-1 in non-degenerated, degenerated or herniated human intervertebral discs (IVDs). The expression of LOX-1 and matrix metalloproteinase 3 (MMP3) were studied after incubating nucleus pulposus cells (NPCs) with ox-LDL. The presence of ox-LDL and LOX-1 was positively related with the extent of IVDD in nucleus pulposus (NP), end-plate cartilage and outer annulus fibrous, but not with the extent of degeneration of inter annulus fibrous. Ox-LDL significantly reduced the viability of human NPCs in a dose and time-dependent manner, and increased the expression of MMP3 induced by LOX-1. Pretreatment with anti-human LOX-1 monoclonal antibody reversed these effects. Ox-LDL, principally mediated by LOX-1, enhanced MMP3 production in NPCs through the NF-κB signaling pathway. In conclusion, increased accumulation of ox-LDL and LOX-1 in IVDs indicates a specific role of the receptor-ligand interaction in degeneration or herniation of IVDs.

Preoperative planning software has been widely used in many other minimally invasive surgeries, but there is a lack of information describing the clinical benefits of existing software applied in percutaneous endoscopic lumbar discectomy (PELD). This study aimed to compare the clinical efficacy of preoperative planning software in puncture and channel establishment of PELD with routine methods in treating lumbar disc herniation (LDH). From June 2016 to October 2016, 40 patients who had single L4/5 or L5/S1 disc herniation were divided into two groups. Group A adopted planning software for preoperative puncture simulation while Group B took routine cases discussion for making puncture plans. The channel establishment time, operative time, fluoroscopic times and complications were compared between the two groups. The surgical efficacy was evaluated according to the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and modified Macnab's criteria. The mean channel establishment time was 25.1 ± 4.2 min and 34.6 ± 5.4 min in Group A and B, respectively (P < 0.05). The mean operative time was 80.8 ± 8.4 min and 92.1 ± 7.3 min in Group A and B, respectively (P < 0.05). The fluoroscopic times were 21.5 ± 5.2 in Group A and 29.3 ± 5.5 in Group B (P < 0.05). There were no significant differences in VAS and ODI scorings between the two groups either preoperatively or postoperatively (P > 0.05). The findings of modified Macnab's criteria at each follow-up also showed no significant differences (P > 0.05). The application of preoperative planning software in puncture and cannula insertion planning in PELD was easy and reliable, and could reduce the channel establishment time, operative time and fluoroscopic times of PELD significantly.

Study design: This was a cross-sectional frequency-matched case–control study. Background and aim: The serum lipid profile of lipoprotein(a) [Lp(a)] level and apolipoprotein B/apolipoprotein A1 ratio (Apo B/Apo A1) ratio were found to be more representative for serum lipid level and were recognized as the independent risk factors for various diseases. Although the blood levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were found to be associated with symptomatic intervertebral disk herniation (IDH), no studies to date have evaluated the association of Apo AI, Apo B, Lp(a), and Apo B/Apo AI levels with symptomatic IDH. This study aimed to assess the link between blood lipid levels and symptomatic IDH. Method: The study included 1839 Chinese patients. Of these, 918 patients were diagnosed with IDH and enrolled in the experimental group. A control group of 921 patients underwent a physical examination during the same period. The serum lipid levels of TC, TG, LDL-C, HDL-C, Lp(a), Apo B, and Apo B/Apo AI were examined and analyzed. The control group comprised randomly selected patients who met the baseline levels of the aforementioned lipid molecules. Results: Patients with IDH exhibited significantly higher TC, TG, LDL, Apo B, and Lp(a) levels than controls. The percentage of high TC, high TG, high LDL, high Apo B, and high Lp(a) were obviously higher in the IDH group than in the control group. However, hyperlipidemia had no relationship with the degenerated segment of the IDH (P = 0.201). The odds ratio (OR) for the incidence of IDH with elevated levels of LDL-C, TC, TG, Lp(a), Apo B, and Apo B/Apo AI was 1.583, 1.74, 1.62, 1.58, 1.49, and 1.39, respectively. The correlation analysis revealed the correlation between elevated LDL-C, TC, TG, Apo B, Lp(a), and incidence of IDH was significant (R²_LDL = 0.017; R²_TC = 0.004; R²_TG = 0.015; R²_{Apo B} = 0.004; R²_Lp(a) = 0.021) (P < 0.05). Conclusion: This study suggested that elevated levels of serum TC, TG, LDL, Apo B, Lp(a), and Apo B/Apo AI were associated with a higher risk of IDH. This study provided useful information to identify a population that might be at risk of developing IDH based on elevated lipid levels.

Background: Intervertebral disk degeneration (IDD) is a degenerative disease that underlies various musculoskeletal and spinal disorders and is positively correlated with age. tRNA-derived small RNAs (tsRNA), as a new small noncoding RNAs, its function in IDD is unclear. Herein, our goal was to find the key tsRNA that affects IDD independently of age and explore the underlying mechanisms. Methods: Small RNA sequencing was performed in nucleus pulposus (NP) tissues of traumatic lumbar fracture individuals, young IDD (IDDY) patients, and old IDD (IDDO) patients. The biological functions of tsRNA-04002 in NP cells (NPCs) were investigated by qRT-PCR, western blot, and flow cytometry analysis. The molecular mechanism of tsRNA-04002 was demonstrated by luciferase assays and rescue experiments. Furthermore, the therapeutic effects of tsRNA-04002 on IDD rat model were used and evaluated in vivo. Results: Compared with fresh traumatic lumbar fracture patients, a total of 695 disordered tsRNAs is obtained (398 down-regulated tsRNAs and 297 up-regulated tsRNAs). These disordered tsRNAs were mainly involved in Wnt signaling pathway and MAPK signaling pathway. tsRNA-04002 was an age-independent key target in IDD, which was both lower expressed in IDDY and IDDO groups than control group. Overexpression of tsRNA-04002 restrained inflammatory cytokines IL-1β and TNF-α expression, increased the COL2A1, and inhibited the NPCs apoptosis. Furthermore, we determined that PRKCA was the target gene of tsRNA-04002 and was negatively regulated by tsRNA-04002. The rescue experiment results suggested that the high expression of PRKCA reversed the inhibitory effect of tsRNA-04002 mimics on NPCs inflammation and apoptosis, and promotive effect of COL2A1. Moreover, tsRNA-04002 treatment dramatically ameliorated the IDD process in the puncture-induced rat model, together with the blockade of PRKCA in vivo. Conclusion: Collectively, our results substantiated that tsRNA-04002 could alleviate IDD by targeting PRKCA to inhibit apoptosis of NPCs. tsRNA-04002 may be a novel therapeutic target of IDD progression.