Identification and verification of a novel signature that combines cuproptosis-related genes with ferroptosis-related genes in osteoarthritis using bioinformatics analysis and experimental validation.

BACKGROUND: Exploring the pathogenesis of osteoarthritis (OA) is important for its prevention, diagnosis, and treatment. Therefore, we aimed to construct novel signature genes (c-FRGs) combining cuproptosis-related genes (CRGs) with ferroptosis-related genes (FRGs) to explore the pathogenesis of OA and aid in its treatment. MATERIALS AND METHODS: Differentially expressed c-FRGs (c-FDEGs) were obtained using R software. Enrichment analysis was performed and a protein-protein interaction (PPI) network was constructed based on these c-FDEGs. Then, seven hub genes were screened. Three machine learning methods and verification experiments were used to identify four signature biomarkers from c-FDEGs, after which gene set enrichment analysis, gene set variation analysis, single-sample gene set enrichment analysis, immune function analysis, drug prediction, and ceRNA network analysis were performed based on these signature biomarkers. Subsequently, a disease model of OA was constructed using these biomarkers and validated on the GSE82107 dataset. Finally, we analyzed the distribution of the expression of these c-FDEGs in various cell populations. RESULTS: A total of 63 FRGs were found to be closely associated with 11 CRGs, and 40 c-FDEGs were identified. Bioenrichment analysis showed that they were mainly associated with inflammation, external cellular stimulation, and autophagy. CDKN1A, FZD7, GABARAPL2, and SLC39A14 were identified as OA signature biomarkers, and their corresponding miRNAs and lncRNAs were predicted. Finally, scRNA-seq data analysis showed that the differentially expressed c-FRGs had significantly different expression distributions across the cell populations. CONCLUSION: Four genes, namely CDKN1A, FZD7, GABARAPL2, and SLC39A14, are excellent biomarkers and prospective therapeutic targets for OA.

Correlation between the spinopelvic type and morphological characteristics of lumbar facet joints in degenerative lumbar spondylolisthesis.

OBJECTIVE: The correlation between the spinopelvic type and morphological characteristics of lumbar facet joints in patients with degenerative lumbar spondylolisthesis (DLS) was investigated. METHODS: One hundred forty-two patients with L4 DLS were enrolled (DLS group), and 100 patients with lumbar disc herniation without DLS were selected as the control group (i.e., non-lumbar spondylolisthesis [NL] group). Morphological parameters of L4-5 facet joints and L4-5 disc height and angle were measured on 3D reconstructed CT images; namely, the facet joint angle (FJA), pedicle-facet joint angle (PFA), facet joint tropism, and facet joint osteoarthritis (OA). The L4 slip percentage, sacral slope, and lumbar lordosis were measured on radiographs. Patients in the DLS and NL groups were divided into 4 subgroups according to Roussouly classification (types I, II, III, and IV). RESULTS: In the DLS and NL groups, as the spinopelvic type changed from type II to type IV, the facet joint morphology showed a gradual sagittal orientation in the FJA, a gradual horizontal orientation in the PFA, a gradual severity in OA, and a gradual increase in the slip percentage, but changes were completely opposite from type I to type II. Additionally, compared with the NL group, the facet joint morphology in the DLS group had more horizontal orientation in PFA, more sagittal orientation in the FJA, and the facet joint tropism and OA were more severe. CONCLUSIONS: Facet joint morphology was correlated with spinopelvic type in the slip segment of DLS. Facet joint morphology was part of the joint configuration in different spinopelvic types, not just the result of joint remodeling after DLS. Moreover, morphological changes of the facet joints and DLS interacted with each other. Additionally, morphological remodeling of the facet joints in DLS played an important role in spinal balance and should be taken into consideration when designing a surgical approach.

Correlation Between Sacral Slope and Pedicle Morphology of the Fourth Lumbar Vertebra in Degenerative Lumbar Spondylolisthesis.

STUDY DESIGN: Retrospective Radiographic Review. OBJECTIVES: The purpose of this study was to investigate the correlation between the sacral slope (SS) and pedicle morphological parameters of the fourth lumbar vertebra in degenerative lumbar spondylolisthesis (DLS). METHODS: Our study included 134 patients with L4-5 DLS. We used preoperative multi-slice spiral computed tomography to measure a range of pedicle morphological parameters, and the SS and percentage of slip distance (SDP) of the L4 vertebra were measured on preoperative standing neutral lumbar radiography. Patients were divided into three groups based on their degree of SS: the low sacral slope (LSS) group with SS values of <35°, the mean sacral slope (MSS) group with SS of 35°-45°, and the high sacral slope (HSS) group with SS > 45°. RESULTS: As the SS increased across groups, the pedicles of L4 became longer and thinner and the pedicle camber angle was smaller. The SDP, pedicle length parameters were positively correlated with the SS, while pedicle width, height, and camber angle were negatively correlated with the SS in the three groups. CONCLUSIONS: SS had an impact on the degree of spondylolisthesis and on pedicle morphological parameters in patients with DLS, with greater slope resulting in greater impact. The progression of DLS occurred due to the increasing forward shear force of the vertebra being greater than the reverse resistance. The pedicle at the slip level adaptively remodeled, becoming slenderer and tilting inward due to the long-term traction of the two opposing forces.