Intervertebral disc degeneration (IVDD), a leading cause of chronic low back pain, arises from nucleus pulposus (NP) cell dysfunction due to oxidative stress‐induced mitophagy impairment and ferroptosis, though regulatory mechanisms remain unclear. F‐box only protein 2 (FBXO2), a Kruppel‐like factor 10 (KLF10)‐regulated F‐box protein, is downregulated in degenerated human NP tissues and correlates with disease severity. Overexpression of FBXO2 restores extracellular matrix (ECM) homeostasis by promoting matrix component synthesis and inhibiting catabolic enzymes, while its knockdown exacerbates ECM degradation. Under oxidative stress, FBXO2 activates PTEN‐induced putative kinase 1 (PINK1)/Parkin‐dependent mitophagy, restoring mitochondrial membrane potential and reducing reactive oxygen species (ROS) accumulation. Proteomics reveals that FBXO2 suppresses ferroptosis by attenuating lipid peroxidation, glutathione depletion, and iron overload. Mechanistically, FBXO2 binds lipocalin‐2 (LCN2) via its FBA domain, promoting K27‐linked polyubiquitination to drive proteasomal degradation of this ferroptosis inducer. FBXO2 co‐expression reverses LCN2‐induced mitochondrial dysfunction and ferroptosis markers. In vivo, adeno‐associated virus 9 (AAV9)‐mediated overexpression of FBXO2 ameliorates IVDD in rats, whereas FBXO2 knockout (KO) mice exhibit exacerbated IVDD. LCN2 silencing in FBXO2‐deficient mice partially restores disc integrity and matrix component expression. These findings identify FBXO2 as a dual regulator coordinating mitophagy activation and ferroptosis suppression, offering therapeutic potential for IVDD progression.

Introduction: Bone tissue engineering is a promising method to treat bone defects. However, the current methods of preparing composite materials that mimic the complex structure and biological activity of natural bone are challenging for recruitment of bone marrow mesenchymal stem cells (BMSCs), which affects the application of these materials in situ bone regeneration. Hollow hydroxyapatite microspheres (HHMs) possess a natural porous bone structure, good adsorption, and slow release of chemokines, but have low ability to recruit BMSCs and induce osteogenesis. In this study, The HHM/chitosan (CS) and recombinant human C-X-C motif chemokine ligand 13 (rhCXCL13)-HHM/CS biomimetic scaffolds that optimize bone regeneration and investigated their mechanism of BMSC recruitment and osteogenesis through cell and animal experiments and transcriptomic sequencing. Methods: Evaluate the physical characteristics of the HHM/CS and rhCXCL13-HHM/CS biomimetic scaffolds through Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), and the cumulative release curve of rhCXCL13. Transwell migration experiments and co-culture with BMSCs were conducted to study the recruitment ability and osteogenic differentiation of the scaffolds. Transcriptomic sequencing was performed to analyze the osteogenic differentiation mechanism. The osteogenesis and bone healing performance were evaluated using a rabbit radial defect model. Results: SEM demonstrated that the rhCXCL13-HHM/CS scaffold comprised hydroxyapatite microspheres in a porous three-dimensional network. The rhCXCL13 showed excellent sustained release capability. The rhCXCL13-HHM/CS scaffold could recruit BMSCs and induce bone regeneration. Transcriptome sequencing and experimental results showed that the osteogenesis mechanism of rhCXCL13-HHM/CS was through the PI3K-AKT pathway. In vivo, the rhCXCL13-HHM/CS scaffold significantly promoted osteogenesis and angiogenesis at 12 weeks after surgery. Conclusion: The rhCXCL13-HHM/CS scaffold demonstrates excellent potential for BMSC recruitment, osteogenesis, vascularized tissue-engineered bone reconstruction, and drug delivery, providing a theoretical basis for material osteogenesis mechanism study and promising clinical applications for treating large bone defects.

Purpose: There has been an association between changes in body composition, fracture incidence, and age in previous studies. Telomere length (TL) has been proposed as a biomarker of aging. However, the relationship between body composition, fractures, and TL has rarely been studied. Therefore, this study aimed to investigate the correlation between TL and body composition and fractures.Patients and methods: 20950 participants from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) were included in the final analysis. In NHANES, body compositions were measured with DXA, and TL was determined with quantitative PCR. Correlation analysis of TL and body composition was conducted using multivariate weighted linear regression and logistic regression models.Results: The results showed that TL positively correlated with bone mineral density (BMD) and bone mineral content (BMC) in most body parts. However, BMD and BMC were negatively connected with TL in the upper limbs and skull. Fat content was negatively associated with TL, while muscle content was positively linked to TL. In addition, TL’s trend analysis results were consistent with the regression model when transformed from a continuous to a classified variable. An increase in TL was associated with a higher incidence of wrist fractures, while a decrease in spine fractures. The above correlation also has a certain degree of sex specificity.Conclusion: Our study indicate that TL is associated with body composition as well as fractures, but further research is needed to confirm these contrasting associations in the skull, upper limbs, and wrists.

Objective: To determine if preoperative albumin-alkaline phosphatase ratio (AAPR) is predictive of clinical outcomes in patients with degenerative lumbar diseases undergoing lumbar fusion. Method: 326 patients undergoing posterior lumbar decompression and fusion were retrospectively analyzed. The cumulative grade was calculated by summing the Pfirrmann grades of all lumbar discs. Grouping was based on the 50th percentile of cumulative grade. The relationship between AAPR, intervertebral disc degeneration (IDD) severity, and fusion rate was explored using correlation analyses and logistic regression models. Meanwhile, the ROC curve evaluated the discrimination ability of AAPR in predicting severe degeneration and non-fusion. Results: High AAPR levels were significantly negatively correlated with severe degeneration and non-fusion rate. A multivariate binary logistic analysis revealed that high preoperative AAPR was an independent predictor of severe degeneration and postoperative non-fusion (OR: 0.114; 95% CI: 0.027–0.482; p = 0.003; OR: 0.003; 95% CI: 0.0003–0.022; p < 0.001). The models showed excellent discrimination and calibration. The areas under the curve (AUC) of severe degeneration and non-fusion identified by AAPR were 0.635 and 0.643. Conclusion: The AAPR can help predict the severity of disc degeneration and the likelihood of non-fusion.

Purpose: Inflammation is integral to the pathogenesis of intervertebral disc degeneration, yet the role of systemic inflammatory markers in this process remains underexplored. This study aims to explore the association between the Neutrophil-to-Lymphocyte Ratio (NLR) and the severity of disc degeneration.Patients and methods: A retrospective analysis was conducted on 375 patients diagnosed with lumbar disc degeneration between April 2018 and May 2021. All patients underwent a complete blood cell count examination. We applied the Pfirrmann grading system for cumulative disc grading, stratifying patients into two groups: a high-score group (cumulative grade > 17) and a low-score group (cumulative grade ≤ 17), based on the median cumulative grade. The association between the NLR and and the severity of disc degeneration was further analyzed using correlation analysis and logistic regression models. Furthermore, the predictive capacity of the NLR for lumbar disc degeneration was assessed using the Receiver Operating Characteristic (ROC) curve.Results: We found a significant positive correlation between high NLR levels and severe disc degeneration. The high-score group exhibited a significantly higher NLR compared to the low-score group [2.63 (1.91–4.18) vs. 2.04 (1.38–2.74), respectively, p < 0.001]. Significant correlations were found between NLR and patient characteristics (including age, BMI, VAS, NSAIDs usage, hemoglobin) and the cumulative grading. Logistic regression analysis identified age and NLR as independent predictors of the severity of disc degeneration. The ROC curve analysis demonstrated a good predictive capability of NLR for lumbar disc degeneration.Conclusion: NLR could serve as a promising biomarker for assessing the severity of lumbar disc degeneration and offer potential benefits in both early diagnosis and treatment strategies.