Correlation analysis of surgical outcomes and spino-pelvic parameters in patients with degenerative lumbar scoliosis.

Objectives: The study aims to analyze factors that affect the postoperative health-related quality of life (HRQOL) of degenerative lumbar scoliosis (DLS) patients and explore the appropriate pelvic incidence minus lumbar lordosis (PI-LL) value for Chinese DLS patients. Methods: DLS patients who met the inclusion and exclusion criteria were included in this study. General information, spino-pelvic parameters, and HRQOL were collected. Correlation analysis was used to explore the spino-pelvic parameters that affect the postoperative HRQOL. Thresholds of each parameter were obtained using the receiver operating characteristic (ROC) curve. Regardless of the effect of age, DLS patients were classified into three groups according to the SRS-Schwab classification: group 0 means PI-LL < 10°, group+means PI-LL = 10-20°, and group ++ means PI-LL > 20°. Postoperative HRQOL was analyzed using variance methods. The ROC curve was used to measure the appropriate PI-LL threshold. When considering the effect of age, the patients with Oswestry Disability Index (ODI) < 75% percentile were considered to have a satisfactory clinical outcome, which was drawn to an equation between PI-LL, age, and PI by multiple linear regression equation. Results: A total of 71 patients were included. Compared with the control group, there were significant differences in both postoperative ODI and Scoliosis Research Society 22 (SRS-22) scores when the postoperative Cobb angle ≤11°, postoperative lumbar lordosis index (LLI) > 0.8, postoperative sagittal vertical axis (SVA) ≤ 5 cm, postoperative T1 pelvic angle (TPA) ≤ 16° and postoperative global tilt (GT) ≤ 22°, respectively. Regardless of the effect of age, there was a statistical difference in postoperative HRQOL between group 0 and group ++. The PI-LL threshold derived from the ROC curve was 14.4°. Compared with the PI-LL > 14° group, the PI-LL ≤ 14° group achieved a lower postoperative ODI score and a higher postoperative SRS-22 score. Considering the influence of age, the equation for ideal PI-LL was PI-LL = 0.52age + 0.38PI-39.4 (R = 0.509, p = 0.001). Conclusions: PI-LL was an important parameter that affects the postoperative HRQOL of DLS patients. Sufficient LL should be restored during the operation (LL ≥ PI-14°). The appropriate PI-LL value was affected by age. Smaller LL needed to be restored as the age increased.

Inverse Agonist of Retinoid-Related Orphan Receptor-Alpha Prevents Apoptosis and Degeneration in Nucleus Pulposus Cells via Upregulation of YAP.

Intervertebral disc degenerative disease (IDD) is the most common degenerative spine disease, which leads to chronic low back pain and symptoms in the lower extremities. In this study, we found that RORα, a member of the retinoid-related orphan receptor family, is significantly elevated in nucleus pulposus tissue in IDD patients. The elevation of RORα is associated with increased apoptosis of nucleus pulposus (NP) cells. Therefore, we applicated a well-established inverse agonist of RORα, SR3335, to investigate its role in regulating NP cell metabolism and apoptosis. To further investigate the mechanism that SR3335 regulates the pathogenesis of IDD in vitro, tumor necrosis factor alpha (TNF-α) stimulation was used in human NP cells to mimic the hostile environment that leads to degeneration. We found that SR3335 treatment reversed the trend of increased apoptosis in NP cells induced by TNF-α treatment. Next, TNF-α treatment upregulated the expression of type II collagen and aggrecan and downregulated MMP13 (matrix-degrading enzyme matrix metalloproteinase 13) and ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4). However, these effects were reversed after SR3335 treatment. Furthermore, we find that SR3335 mediated the effect in NP cells by regulating the YAP signaling pathway, especially by affecting the phosphorylation state of YAP. In conclusion, the reduction of matrix degradation enzymes and apoptosis upon SR3335 treatment suggests that SR3335 is a promising drug in reversing the deleterious microenvironment in IDD patients.

Melatonin promotes bone marrow mesenchymal stem cell osteogenic differentiation and prevents osteoporosis development through modulating circ_0003865 that sponges miR-3653-3p.

BACKGROUND: Little is known about the implications of circRNAs in the effects of melatonin (MEL) on bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation and osteoporosis (OP) progression. The aim of our study was to investigate circRNAs in MEL-regulated BMSC differentiation and OP progression. METHODS: BMSC osteogenic differentiation was measured by qRT-PCR, western blot (WB), Alizarin Red, and alkaline phosphatase (ALP) staining. Differential circRNA and mRNA profiles of BMSCs treated by MEL were characterized by deep sequencing, followed by validation using RT-PCR, Sanger sequencing, and qRT-PCR. Silencing and overexpression of circ_0003865 were conducted for functional investigations. The sponged microRNAs and targeted mRNAs were predicted by bioinformatics and validated by qRT-PCR, RNA pull-down, and dual-luciferase reporter assay. The function of miR-3653-3p and circ_0003865/miR-3653-3p/growth arrest-specific gene 1 (GAS1) cascade was validated for the osteogenic differentiation of BMSCs by CCK-8, qRT-PCR, WB, Alizarin Red, and ALP staining. The effects of circ_0003865 on OP development were tested in murine OP model. RESULTS: MEL promoted osteogenic differentiation of BMSCs. RNA sequencing revealed significant alterations in circRNA and mRNA profiles associated with multiple biological processes and signaling pathways. Circ_0003865 expression in BMSCs was significantly decreased by MEL treatment. Silencing of circ_0003865 had no effect on proliferation while promoted osteogenic differentiation of BMSCs. Overexpression of circ_0003865 abrogated the promotion of BMSC osteogenic differentiation induced by MEL, but proliferation of BMSCs induced by MEL had no change whether circ_0003865 was overexpression or not. Furthermore, circ_0003865 sponged miR-3653-3p to promote GAS1 expression in BMSCs. BMSC osteogenic differentiation was enhanced by miR-3653-3p overexpression while BMSC proliferation was not affected. By contrast, miR-3653-3p silencing mitigated the promoted BMSC osteogenic differentiation caused by circ_0003865 silencing, but had no effect on proliferation. Finally, circ_0003865 silencing repressed OP development in mouse model. CONCLUSION: MEL promotes BMSC osteogenic differentiation and inhibits OP pathogenesis by suppressing the expression of circ_0003865, which regulates GAS1 gene expression via sponging miR-3653-3p.