Exploration of microRNA-106b-5p as a therapeutic target in intervertebral disc degeneration: a preclinical study.

MicroRNA (miRNA) has emerge as a vital regulator in the pathogenesis of intervertebral disc degeneration (IDD). However, miR-106b-5p expression in the human nucleus pulposus (NP) and potential mechanisms remain to be elucidated. In this study, the aim was to verify the potential therapeutic mechanisms of miR-106b-5p for IDD. Key miRNAs were screened for in degenerative and normal human intervertebral disc samples. qRT-PCR and fluorescence in situ hybridization (FISH) were used to verify the miR-106b-5p differential expression. The targeting link between miR-106b-5p and Sirtuin 2 (SIRT2) was identified using the luciferase reporter assay and bioinformatics. Flow cytometry, EdU method, and cell scratching were all performed to determine the NP cell function and IDD models were constructed for in vivo experiments. SIRT2, MMP13, ADAMTS5, Col II, Aggrecan, Ras, ERK1/2, and p-ERK1/2 protein levels were assayed by western blotting. Overexpression of miR-106b-5p in NP cells decreased cell growth, induced apoptosis, hindered extracellular matrix formation, and increased the expression of matrix-degrading enzymes through the SIRT2/MAPK/ERK signaling pathway. Importantly, intradiscal delivery of antagomiR-106b-5p significantly attenuated IDD development. Our findings demonstrate that targeting miR-106b-5p in intervertebral disc has therapeutic effects on IDD.

Gene locus polymorphisms and expression levels of interleukin-1 in lumbar disc disease: A MOOSE-compliant meta-analysis and immunohistochemical study.

OBJECTIVE: To investigate the association between interleukin (IL)-1α (rs1800587), IL-1ß (rs1143634) and IL-1 receptor antagonist (RN) variable number tandem repeat polymorphisms, expression levels and lumbar disc disease (LDD). METHODS: All relevant articles were searched from 4 databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to evaluate the association between IL-1 gene locus polymorphisms (rs1800587 in IL-1α, rs1143634 in IL-1ß, variable number tandem repeat in interleukin-1 receptor antagonist) and LDD susceptibility. Statistical analysis was conducted by Review Manager (Revman) 5.31 software (Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark). Furthermore, qRT-PCR and immunohistochemistry were performed to evaluate IL-1α, IL-1ß and interleukin-1 receptor antagonist expressions in the normal and degenerated disc. RESULTS: A total of 15 case-control studies (1455 cases and 2362 controls) were included in our meta-analysis. The pooled results suggested that IL-1α rs1800587 polymorphism was associated with an increased risk of LDD in overall population (T vs. C, OR = 1.21, 95% CI = 1.04-1.40, P = .01). The subgroup analysis found a significant association between IL-1ß rs1143634 polymorphism and LDD in Asian population (T vs. C, OR = 0.61, 95% CI = 0.39-0.96, P = .03). Results of qRT-PCR and immunohistochemistry demonstrated that expressions of IL-1α and IL-1ß were significantly increased in the degenerated disc. (all P < .05). CONCLUSION: IL-1α rs1800587 and IL-1ß rs1143634 polymorphisms were significantly associated with LDD in overall population and in Asian population, respectively. The increased expression levels of IL-1α and IL-1ß may be the important risk factors for LDD.

Surgical resection of intradural extramedullary tumors in the atlantoaxial spine via a posterior approach.

BACKGROUND: The anatomical features of the atlantoaxial spine increase the difficulty of complete and safe removal of atlantoaxial intradural extramedullary (IDEM) tumors. Studies concerning surgical interventions via a posterior approach are limited. AIM: To investigate the safety and efficacy of atlantoaxial IDEM tumor resection using a one-stage posterior approach. METHODS: We retrospectively analyzed clinical databases for one-stage atlantoaxial IDEM tumor resection via a posterior approach between January 2008 and January 2018. The analyzed data included tumor position, histopathological type, pre- and post-operative Japanese Orthopedic Association (JOA) scores and Nurick grades, postoperative complication and recurrence status. RESULTS: A total of 13 patients who underwent C1-C2 Laminectomy and/or unilateral facetectomy via the posterior approach were enrolled in the study. In all cases reviewed, total tumor resection and concomitant C1-C2 fusion were achieved. The average follow-up was 35.3 ± 6.9 mo (range, 26-49 mo). A statistically significant difference was noted between the preoperative JOA score (11.2 ± 1.1) and the score at the last final follow-up (15.6 ± 1.0) (P < 0.05). A statistically significant difference was noted between the preoperative Nurick grade (2.3 ± 0.9) and that at the last follow-up (1.2 ± 0.4) (P < 0.05). However, no statistically significant difference was noted between the preoperative and last follow-up C1-2 Cobb angle and C2-7 Cobb angle (P > 0.05). No mortalities, severe complications or tumor recurrence were observed during the follow-up period. CONCLUSION: Total resection of atlantoaxial IDEM tumors is feasible and effective via a posterior approach. Surgical reconstruction should be considered to avoid iatrogenic kyphosis and improve spinal stability and overall clinical outcomes.