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.

Aneurysmal bone cyst secondary to giant cell tumor of the extremities: a case series of 30 patients.

The purpose was to investigate the clinical features, diagnosis, treatment, and prognosis of aneurysmal bone cyst (ABC) secondary to giant cell tumors (GCT) of the extremities. Data from patients with ABC secondary to GCT of the extremities were obtained from the medical records. Clinical features, imaging findings, pathologic diagnosis, surgical methods, and prognosis were analyzed. The median age of the patients was 33 years (range 15 to 52 years) and 83.3 percent were between 20 to 40 years. The lesions were mainly located in the proximal tibia and distal femur, accounting for 63.3% (19/30). 21 patients were treated with curettage, and 9 with tumor resection. The recurrence rates of the curettage group and resection group were 52.4% and 11.1% respectively. However, the average postoperative (Musculoskeletal Tumor Society) MSTS score were 28.6±1.2 post-curettage, and 25.0±0.5 post-resection, with a significant difference between the 2 groups (P<0.01). In these relapsed patients, 10 underwent a second curettage, while 2 cases underwent a resection and there was no postoperative re-recurrence in both groups. A comprehensive analysis should be performed when making the diagnosis of ABC secondary to GCT. Although the recurrence rate is higher, curettage is still the optimal method for satisfactory joint function. If recurrence occurs after the first curettage, a second curettage should be performed.

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.

MicroRNA-338-3p as a novel therapeutic target for intervertebral disc degeneration.

Recent studies have demonstrated the pivotal role played by microRNAs (miRNAs) in the etiopathogenesis of intervertebral disc degeneration (IDD). The study of miRNA intervention in IDD models may promote the advancement of miRNA-based therapeutic strategies. The aim of the current study was to investigate whether intradiscal delivery of miRNA can attenuate IDD development. Our results showed that miR-338-3p expression was significantly increased in the nucleus pulposus (NP) of patients with IDD. Moreover, there was a statistically significant positive correlation between the expression level of miR-338-3p and the severity of IDD. Our functional studies showed that miR-338-3p significantly influenced the expression of extracellular matrix synthesis genes, as well as the proliferation and apoptosis of NP cells. Mechanistically, miR-338-3p aggravated IDD progression by directly targeting SIRT6, a negative regulator of the MAPK/ERK pathway. Intradiscal injection of antagomir-338-3p significantly decelerated IDD development in mouse models. Our study is the first to identify miR-338-3p as a mediator of IDD and thus may be a promising target for rescuing IDD.

Two GWAS-identified variants are associated with lumbar spinal stenosis and Gasdermin-C expression in Chinese population.

The aim of this study is to investigate the expression levels of genome-wide association studies (GWAS)-identified variants near Gasdermin-C (GSDMC) and its association with lumbar disc degeneration (LDD) in a Chinese population. In accordance with previously reported findings, our study involved the top 4 variants; rs6651255, rs7833174, rs4130415, and rs7816342. A total of 800 participants, 400 LDD patients and 400 controls were involved in the study. The LDD patients were divided into two mutually exclusive subgroups: subgroup 1: lumbar disc herniation; subgroup 2: lumbar spinal stenosis. Genotyping were performed using TaqMan assay, and Enzyme-Linked Immunosorbent Assay (ELISA) used to measure the plasma GSDMC levels, while quantitative reverse-transcription (qRT)-PCR and immunohistochemistry (IHC) were used to evaluate the GSDMC expression levels. Among the studied variants, there were no statistically significant differences in allelic and genotypic frequencies between LDD patients and their controls (all P > 0.05). However, the subgroup analysis revealed a significant association between rs6651255 and rs7833174 in patients with lumbar spinal stenosis (subgroup 2). Furthermore, the max-statistic test revealed that the inheritance models of two variants of lumbar spinal stenosis were represented by the recessive model. The plasma and mRNA expression levels of GSDMC were significantly higher in patients with lumbar spinal stenosis compared with the control group (P < 0.05). Furthermore, the CC genotypes of rs6651255 and rs7833174 were significantly associated with increased plasma expression levels of GSDMC in patients with lumbar spinal stenosis (P < 0.01). Two GWAS-identified variants (rs6651255 and rs7833174) near GSDMC were associated with a predisposition to lumbar spinal stenosis. GSDMC protein and mRNA expression levels may have prognostic qualities as biomarkers for the existence, occurrence or development of lumbar spinal stenosis.

Gene polymorphisms and expression levels of interleukin-6 and interleukin-10 in lumbar disc disease: a meta-analysis and immunohistochemical study.

BACKGROUND: To investigate the association between interleukin-6 (IL-6) (rs1800795, rs1800796, rs1800797, rs13306435, rs2069849) and interleukin-10 (IL-10) (rs1800871, rs1800896) gene polymorphisms, expression levels, and lumbar disc disease (LDD). METHODS: We conducted a literature research on PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) until February 28, 2019. We included all case-control studies about the association between IL-6 and IL-10 gene polymorphisms and LDD. The odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of association. Statistical analysis was conducted by Review Manager (RevMan) 5.3 software. Furthermore, immunohistochemistry (IHC) and RT-PCR were performed to evaluate IL-6 and IL-10 expressions in the normal and degenerated disc. RESULTS: A total of 6 studies, involving 1456 cases and 1611 controls, were included in this meta-analysis. G alleles of rs1800795 and rs1800797 in the IL-6 gene were significantly associated with LDD (rs1800795: G vs. C, OR = 1.38, 95% CI = 1.16-1.64, P = 0.0002; rs1800797: G vs. A, OR = 1.35, 95% CI = 1.14-1.61, P = 0.0006). Begg's funnel plot and Egger's tests did not show any evidence of publication bias. IL-6 expression and IL-6 mRNA levels were significantly increased in the degenerated disc compared with those in the normal disc (IL-6 immunopositive cells, 73.68 ± 10.99% vs. 37.23 ± 6.42%, P < 0.001). CONCLUSIONS: IL-6 gene polymorphisms (rs1800795 and rs1800797) were significantly associated with susceptibility to LDD. A high expression level of IL-6 may be an important risk factor for LDD.