Intervertebral disc degeneration (IDD) is one of the most common degenerative diseases all over the world. A growing number of studies have proved that large amounts of cytokines are produced during the development of IDD, and the inflammatory responses induced by these cytokines aggravate the occurrence and development of the disc degeneration. In this retrospective single-center study, a total of 182 lumbar spine cases were retrospectively reviewed between July 2020 and October 2021. An appropriate cutoff value was found for discriminating severity of IDD by William rank-sum test and locally weighted scatterplot smoothing algorithm. The cumulative grade was also calculated by summing Pfirrmann grades for all lumbar spine intervertebral discs. It was found that high-score group (total ) plasma interleukin-6 (IL-6) concentration was significantly higher than that of the low-score group (total ) ( vs. pg/ml, ), tumor necrosis factor-α (TNF-α) following the same trend ( vs. , ), which was most pronounced in the upper lumbar intervertebral discs (L1-3). In the entire sample, preoperative IL-6 concentration was significantly higher than that of the postoperation ( ), while the TNF-α was the opposite ( ). It was also found that there were significant differences in the two groups with respect to age and hypertension ( and ). In conclusion, this study preliminarily indicated the relationship between IL-6 and TNF-α and the severity of lumbar disc degeneration.

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.

Intervertebral disc degeneration (IDD) represents a complex pathological process involving impaired cellular homeostasis and extracellular matrix dysregulation. This study elucidates a previously unrecognized regulatory axis wherein angiotensin‐converting enzyme (ACE) modulates prosaposin (PSAP) stability through coordinated post‐translational modifications. Mechanistically, ACE deficiency enhances O ‐GlcNAc transferase (OGT)‐mediated glycosylation of PSAP at critical serine residues, which in turn suppresses E3 ubiquitin ligase Casitas B‐lineage lymphoma (CBL)‐dependent ubiquitination and proteasomal degradation. The stabilized PSAP protein engages G protein‐coupled receptor 37 (GPR37) on macrophages to promote anti‐inflammatory M2 polarization through ERK/SMAD2/3 signaling cascades, while concomitantly stimulating transforming growth factor‐β (TGFβ) secretion. This paracrine signaling establishes a reciprocal regulatory loop, as secreted TGFβ reinforces PSAP‐Sortilin mediated trafficking in nucleus pulposus cells via PI3K/AKT pathway activation. In vivo therapeutic intervention using engineered PSAP and GPR37 gene‐editing virus‐loaded hydrogels demonstrated significant improvements in disc structural integrity and matrix composition in preclinical IDD models, with these protective effects being dependent on GPR37 receptor activation. The findings reveal the ACE‐PSAP‐GPR37 axis as a fundamental regulatory circuit in disc homeostasis, providing new insights into the molecular pathogenesis of IDD while establishing a conceptual framework for targeted therapeutic development.

Intervertebral disc degeneration (IDD) is a major cause of low back pain, yet the biological effects of commonly used non‐steroidal anti‐inflammatory drugs (NSAIDs) on disc cells remain poorly understood. Celecoxib is widely prescribed for IDD‐related pain, but its direct influence on IDD has not been systematically examined. Here, we identify a concentration‐dependent biphasic effect of celecoxib on nucleus pulposus (NP) cells and uncover the mechanism that converts celecoxib from protective to detrimental. Using interleukin‐1β‐stimulated NP cells and rat IDD models, we show that low‐dose celecoxib (≤20 µ m ) suppresses inflammation and preserves extracellular matrix (ECM). In contrast, high‐dose celecoxib (>20 µ m ) activates a previously unrecognized heat shock protein 90 (HSP90)/RING‐box protein 1 (RBX1)/cuproptosis axis, leading to copper accumulation, mitochondrial stress, and ECM degradation. Mechanistically, elevated celecoxib induces HSP90 upregulation, which stabilizes RBX1 by reducing its K48‐linked ubiquitination. Accumulated RBX1 promotes ATPase copper transporting beta (ATP7B) and its regulator copper metabolism domain containing 1 (COMMD1) degradation, thereby triggering cuproptosis. Pharmacologic inhibition of HSP90 or cuproptosis effectively reverses the detrimental effects of high‐dose celecoxib in vivo. Together, these findings define a strict therapeutic window for celecoxib in IDD and reveal a novel HSP90/RBX1‐mediated cuproptosis pathway that mediates its dual effects.

Background: The relation between preoperative cervical disc degeneration and cervical fusion after anterior cervical discectomy and fusion (ACDF) remains unclear. Methods: We reviewed patients who received ACDF from 2019 to 2021. The Pfirrmann grading system was applied to six cervical discs (C2–T1) based on preoperative magnetic resonance imaging. The total degeneration score of six cervical discs was calculated as D Score. A mean degeneration score of operative cervical discs (Mean Surgery D Score) was calculated by dividing the total degeneration score of operative cervical discs by the number of operative segments. Postoperative computed tomography (CT) scans were conducted to determine the result of cervical fusion. Univariate and multivariate logistic regressions were used to explore the risk factors for cervical fusion failure. The receiver operating characteristic (ROC) curves were drawn according to multivariate results. Results: There were 159 patients in the nonfusion group and 135 patients in the fusion group. Univariate logistic regression showed that age, smoking, hypertension, coronary heart disease (CHD), D Score, and Mean Surgery D Score were associated with fusion failure. Hemoglobin, total protein, and albumin were associated with higher fusion rates. D Score (odds ratio [OR]: 1.887, 95%CI: 1.448–2.458, p = 0.001) and Mean Surgery D Score (OR: 8.827, 95%CI: 1.989–39.163, p = 0.004) were independent risk factors of fusion failure. The areas under the ROC curve of D Score and Mean Surgery D Score were 0.904 and 0.875, respectively. Conclusions: Patients with a higher preoperative D Score (> 23.5) and Mean Surgery D Score (> 4.125) have a higher risk of fusion failure after ACDF.