DSCR1-1 attenuates osteoarthritis-associated chondrocyte injury by regulating the CREB1/ALDH2/Wnt/ß-catenin axis: An in vitro and in vivo study.

The progression of osteoarthritis (OA) includes the initial inflammation, subsequent degradation of the extracellular matrix (ECM), and chondrocyte apoptosis. Down syndrome candidate region 1 (DSCR1) is a stress-responsive gene and expresses in varied types of cells, including chondrocytes. Bioinformatics analysis of GSE103416 and GSE104739 datasets showed higher DSCR1 expression in the inflamed cartilage tissues and chondrocytes of OA. DSCR1 had two major isoforms, isoform 1 (DSCR1-1) and isoform 4 (DSCR1-4). We found that DSCR1-1 had a faster (in vitro) and higher expression (in vivo) response to OA compared to DSCR1-4. IL-1ß-induced apoptosis, inflammation, and ECM degradation in chondrocytes were attenuated by DSCR1-1 overexpression. DSCR1-1 triggered the phosphorylation of cAMP response element-binding 1 (CREB1) at 133 serine sites by decreasing calcineurin activity. Moreover, activated CREB1 moved into the cell nucleus and combined in the promoter regions of aldehyde dehydrogenase 2 (ALDH2), thus enhancing its gene transcription. ALDH2 could recover Wnt/ß-catenin signaling transduction by enhancing phosphorylation of ß-catenin at 33/37 serine sites and inhibiting the migration of ß-catenin protein from the cellular matrix to the nucleus. In vivo, adenoviruses (1 × 108 PFU) overexpressing DSCR1-1 were injected into the articular cavity of C57BL/6 mice with medial meniscus surgery-induced OA, and it showed that DSCR1-1 overexpression ameliorated cartilage injury. Collectively, our study demonstrates that DSCR1-1 may be a potential therapeutic target of OA.

A New Automated AI-Assisted System to Assess Cervical Disc Herniation.

STUDY DESIGN: An algorithm was developed with MATLAB platform to automatically quantify the volume of cervical disc herniation (CDH) based on the sagittal magnetic resonance images. This automated program was used for CDH data set, and then compared with manual measurement results confirming its reliability. OBJECTIVE: The aim was to develop a new software for automated CDH volume measurement. SUMMARY OF BACKGROUND DATA: CDH compresses the spinal cord, regarding as the leading cause of cervical myelopathy. However, the CDH volume, of great value to clinical symptoms, can be only manually measured with no-excellent but acceptable interobserver reliability. This was due to the manual error of outlining CDH area and inclusion of structure posterior vertebra. No studies has proposed such an automated algorithm of CDH volume quantification which is standardised to quantify the accurate volume of CDH thus helping doctors easily evaluate CDH progressing. METHODS: The algorithm of CDH volume measurement was proposed. This program was then tested for 490 CDHs data set, from 185 patients with two repeated magnetic resonance imaging detections. Three individual observers manually measured the volumes of these CDHs, to justify the accuracy of this software. CDH volume was either in the classic way or the revised way excluding the influence of structure posterior vertebra. RESULTS: The automated software was successfully developed on MATLAB platform, with no difference found with manual measurements (average level) in CDH volume measurement. The change ratios in CDH volumes were profoundly consistent with manual observation, showing the error of 5.8% in median. The revised method elevated the absolute value of ratio by amplifying the percentage change. CONCLUSION: Our developed automated volumetry system was an standardized and accurate way, with selective removal module of structure posterior vertebra, replaceable for manual volume measurement of CDH, which was useful for spinal surgeons diagnosing and treating CDH disease.

Mesenchymal Stem Cell Derived Exosomes Suppress Neuronal Cell Ferroptosis Via lncGm36569/miR-5627-5p/FSP1 Axis in Acute Spinal Cord Injury.

Exosomes derived from mesenchymal stem cells (MSCs) have been considered as an alternative for cell therapy of acute spinal cord injury (ASCI). However, the underlying mechanism remains unclear. Here, ASCI mouse model and hypoxic cell model were established to evaluate the effects of MSCs and MSCs-derived exosomes (MSCs-exo). The results showed that both MSCs and MSCs-exo inhibited the production of ROS and ferrous iron, upregulated the expression of ferroptosis suppressor FSP1, and enhanced repair of neurological function in the ASCI mice. Besides, MSCs and MSCs-exo attenuated hypoxia-induced neuronal cell ferroptosis and increased cell proliferation. Further study demonstrated that lncGm36569 was enriched in the MSCs-exo. Through bioinformatics analysis and luciferase assay, we confirmed that lncGm36569 acted as a competitive RNA of miR-5627-5p to induce FSP1 upregulation. Furthermore, overexpression of miR-5627-5p reversed the therapeutic effects of lncGm36569 on neuronal cell ferroptosis. In conclusion, MSCs-exosomes lncGm36569 inhibited neuronal cell ferroptosis through miR-5627-5p/FSP1 axis, thereby attenuating neuronal dysfunction.

Volumetric Changes in Cervical Disc Herniation: Comparison of Cervical Expansive Open-door Laminoplasty and Cervical Microendoscopic Laminoplasty.

STUDY DESIGN: Retrospective study on 185 patients with 490 cervical disc herniation (CDH). OBJECTIVE: The aim of this study was to compare the changes in volumes of CDH in patients with degenerative cervical myelopathy (DCM) surgically treated by expansive open-door laminoplasty (EOLP) or cervical microendoscopic laminoplasty (CMEL). SUMMARY OF BACKGROUND DATA: Spontaneous resorption of CDH was shown in patients with DCM after conservation treatment, but very few in surgically treated patients. Our previous study identified the clinical efficiency of CMEL to treat DCM but how CDH sized postoperatively, as well as comparing to EOLP, was unknown. METHODS: Consecutive patients with DCM from December 2015 to December 2019, who underwent MRI evaluation, receiving CMEL or EOLP, and repeat MRI in follow-up were included. The volume of CDH were monitored using the picture archiving and communication system, further calculating the incidence of CDH with volume regression and the percentage changes of CDH volume. The correlations of possible determines with CDH volume changes were analyzed by Spearman rank correlation coefficient. RESULTS: A total of 89 patients (215 CDHs, EOLP-group) and 96 patients (275 CDHs, CMEL-group) was surveyed, respectively. Resultantly, volume of CDH was decreased postoperatively in both EOLP and CMEL cases. But this CDH volume regression was more profound in CMEL groups (incidence of 81.2% from 223/275, median volume change ratio of -26.7%, occurring from 1 month after CMEL), statistically different from EOLP group (50.2% from 108/215, median volume change ratio of -5.4%, none-appearance within 1 month). Patients information as sex, age, and follow-up time, not CDH significant, was significantly correlated with CDH volume changes. CONCLUSION: Patients who underwent CMEL developed a postoperative reduction of CDH volume, with more popularity, greater degree and earlier-staged than EOLP-patients. Young females with longer follow-up time were more likely occur.Level of Evidence: 4.

LncRNA MIAT activates vascular endothelial growth factor A through RAD21 to promote nerve injury repair in acute spinal cord injury.

BACKGROUND: The main pathological feature of acute spinal cord injury (ASCI) is neuronal apoptosis and Long non-coding RNA (lncRNA) myocardial infarction-related transcript (MIAT) is involved in the regulation of neuronal apoptosis. This study aimed to investigate the role and potential mechanism of LncRNA MIAT in neuronal apoptosis induced by ASCI. METHODS: After Lenti-MIAT lentivirus was microinjected into ASCI rats, Basso, Beattie and Bresnahan Score, Hematoxylin-eosin staining, TUNEL staining, immunohistochemical, immunofluorescence, quantitative real-time PCR and Western blot were used to observe the effect of LncRNA MIAT on the nerve function of ASCI rats. MTT and flow cytometry assays were used to identify the in vitro function of LncRNA MIAT. RNA immunoprecipitation, RNA pull-down, Cycloheximide chase and Chromatin immunoprecipitation combined with qPCR experiments were used to study the mechanism. RESULTS: The overexpression of LncRNA MIAT was conducive to the recovery of motor function in ASCI rats and repressed neuronal cell apoptosis and increased neuronal cell viability. Furthermore, the overexpression of LncRNA MIAT in PC12 cells upregulated RAD21 expression by repressing RAD21 protein degradation and further promoted VEGFA transcription to inhibit neuronal cell apoptosis, ultimately improved ASCI. CONCLUSION: Our data indicated that the overexpression of LncRNA MIAT activated VEGFA through RAD21 to inhibit neuronal cell apoptosis in ASCI.

Primary Cilia as a Biomarker in Mesenchymal Stem Cells Senescence: Influencing Osteoblastic Differentiation Potency Associated with Hedgehog Signaling Regulation.

Bone tissue engineering-based therapy for bone lesions requires the expansion of seeding cells, such as autologous mesenchymal stem cells (MSCs). A major obstacle to this process is the loss of the phenotype and differentiation capacity of MSCs subjected to passage. Recent studies have suggested that primary cilia, primordial organelles that transduce multiple signals, particularly hedgehog signals, play a role in senescence. Therefore, we explored the relationships among senescence, primary cilia, and hedgehog signaling in MSCs. Ageing of MSCs by expansion in vitro was accompanied by increased cell doubling time. The osteogenic capacity of aged MSCs at passage 4 was compromised compared to that of primary cells. P4 MSCs exhibited reductions in the frequency and length of primary cilia associated with decreased intensity of Arl13b staining on cilia. Senescence also resulted in downregulation of the expression of hedgehog components and CDKN2A. Suppression of ciliogenesis reduced the gene expression of both Gli1, a key molecule in the hedgehog signaling pathway and ALP, a marker of osteoblastic differentiation. This study demonstrated that the senescence of MSCs induced the loss of osteoblastic differentiation potency and inactivated hedgehog signaling associated with attenuated ciliogenesis, indicating that primary cilia play a mediating role in and are biomarkers of MSC senescence; thus, future antisenescence strategies involving manipulation of primary cilia could be developed.