The study investigates molecular changes in the lumbosacral (L/S) spine's yellow ligamentum flavum during degenerative stenosis, focusing on the role of transforming growth factor beta 1-3 (TGF-β-1-3). Sixty patients with degenerative stenosis and sixty control participants underwent molecular analysis using real-time quantitative reverse transcription reaction technique (RTqPCR), enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemical analysis (IHC). At the mRNA level, study samples showed reduced expression of TGF-β-1 and TGF-β-3, while TGF-β-2 increased by only 4%. Conversely, at the protein level, the study group exhibited significantly higher concentrations of TGF-β-1, TGF-β-2, and TGF-β-3 compared to controls. On the other hand, at the protein level, a statistically significant higher concentration of TGF-β-1 was observed (2139.33 pg/mL ± 2593.72 pg/mL vs. 252.45 pg/mL ± 83.89 pg/mL; p < 0.0001), TGF-β-2 (3104.34 pg/mL ± 1192.74 pg/mL vs. 258.86 pg/mL ± 82.98 pg/mL; p < 0.0001), TGF-β-3 (512.75 pg/mL ± 107.36 pg/mL vs. 55.06 pg/mL ± 9.83 pg/mL, p < 0.0001) in yellow ligaments obtained from patients of the study group compared to control samples. The study did not establish a significant correlation between TGF-β-1-3 concentrations and pain severity. The findings suggest that molecular therapy aimed at restoring the normal expression pattern of TGF-β-1-3 could be a promising strategy for treating degenerative stenosis of the L/S spine. The study underscores the potential therapeutic significance of addressing molecular changes at the TGF-β isoforms level for better understanding and managing degenerative spinal conditions.

This study investigated the role of brain-derived neurotrophic factor (BDNF) in patients with degenerative lumbar stenosis, focusing on its expression and correlation with pain intensity. The study examined 96 patients with lumbar stenosis and 85 control participants. BDNF levels in the yellow ligamentum flavum were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and western blot analysis. The results showed significantly higher BDNF expression at both messenger ribonucleic acid (mRNA; fold change = +1.35 ± 0.23; p < 0.05) and protein levels in patients (28.98 ± 6.40 pg/mg) compared to controls (4.56 ± 1.98 pg/mg; p < 0.05). Furthermore, BDNF levels correlated positively with pain intensity reported by patients, with higher expression observed in those experiencing more severe pain. The study also explored the influence of lifestyle factors, such as smoking and alcohol consumption, and related diseases, such as diabetes, on BDNF expression. Smoking, alcohol use, and diabetes were associated with significantly elevated BDNF levels ( p < 0.05). These findings suggest that BDNF could serve as a biomarker for pain severity in degenerative lumbar stenosis at the protein level, although this was not consistently observed at the mRNA level; this highlights the potential for BDNF-targeted therapies in managing pain. Future research should involve larger longitudinal studies to validate these findings and explore therapeutic interventions. This study underscores the importance of considering molecular and lifestyle factors in the treatment of degenerative lumbar stenosis, aiming to improve patient outcomes through comprehensive, targeted approaches.

The purpose of this study was to evaluate the feasibility of using the expression profile of transforming growth factor beta (TGF-β-1-3) to assess the progression of L/S spine degenerative disease. The study group consisted of 113 lumbosacral (L/S) intervertebral disc (IVD) degenerative disease patients from whom IVDs were collected during a microdiscectomy, whereas the control group consisted of 81 participants from whom IVDs were collected during a forensic autopsy or organ harvesting. Hematoxylin and eosin staining was performed to exclude degenerative changes in the IVDs collected from the control group. The molecular analysis consisted of reverse-transcription real-time quantitative polymerase chain reaction (RT-qPCR), an enzyme-linked immunosorbent assay (ELISA), Western blotting, and an immunohistochemical analysis (IHC). In degenerated IVDs, we noted an overexpression of all TGF-β-1-3 mRNA isoforms with the largest changes observed for TGF-β3 isoforms (fold change (FC) = 19.52 ± 2.87) and the smallest for TGF-β2 (FC = 2.26 ± 0.16). Changes in the transcriptional activity of TGF-β-1-3 were statistically significant (p < 0.05). Significantly higher concentrations of TGF-β1 (2797 ± 132 pg/mL vs. 276 ± 19 pg/mL; p < 0.05), TGF-β2 (1918 ± 176 pg/mL vs. 159 ± 17 pg/mL; p < 0.05), and TGF-β3 (2573 ± 102 pg/mL vs. 152 ± 11 pg/mL) were observed in degenerative IVDs compared with the control samples. Determining the concentration profiles of TGF-β1-3 appears to be a promising monitoring tool for the progression of degenerative disease as well as for evaluating its treatment or developing new treatment strategies with molecular targets.

Background: Degenerative spinal stenosis is a common condition associated with structural degeneration and pain, yet its molecular underpinnings remain incompletely understood. Growth-associated protein 43 (GAP-43), a key player in neuronal plasticity and regeneration, may serve as a biomarker for disease progression and pain severity. This study investigates the expression of GAP-43 at the mRNA and protein levels in the ligamentum flavum of affected patients. Methods: Samples were collected from 96 patients with degenerative spinal stenosis and 85 controls. GAP-43 mRNA expression was analyzed using reverse transcription–quantitative polymerase chain reaction (RT-qPCR), while protein levels were quantified via enzyme-linked immunosorbent assay (ELISA) and Western blot. Pain severity was assessed using the visual analog scale (VAS), and associations with lifestyle factors were analyzed. Results: GAP-43 mRNA expression was significantly downregulated in the study group compared to the controls (fold change = 0.58 ± 0.12, p < 0.05), with an inverse correlation to VAS pain severity (fold change = 0.76 at VAS 4 vs. 0.36 at VAS 10). Conversely, GAP-43 protein levels were markedly elevated in the study group (5.57 ± 0.21 ng/mL) when compared to controls (0.54 ± 0.87 ng/mL, p < 0.0001). Protein levels were also correlated with lifestyle factors, including smoking and alcohol consumption (p < 0.05). Conclusions: GAP-43 shows potential as a biomarker for pain severity and disease progression in degenerative spinal stenosis, in a manner influenced by lifestyle factors. Further research is needed to explore its diagnostic and therapeutic applications.

Background/Objectives: Lumbosacral spinal stenosis (LSS) is a degenerative condition characterized by narrowing of the spinal canal and associated neuropathic pain. While mechanical compression is well-characterized, the molecular mechanisms contributing to symptom severity remain poorly understood. Neurturin (NRTN), a member of the glial cell line-derived neurotrophic factor family, has emerged as a potential mediator of neural plasticity and nociception, but its role in spinal stenosis is largely unexplored. Methods: We analyzed NRTN mRNA and protein expression in ligamentum flavum samples from 96 patients undergoing surgery for LSS and 85 non-degenerative postmortem controls. Quantification was performed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. Pain severity Visual Analog Scale (VAS), body mass index (BMI), diabetes, smoking, and alcohol use were assessed as modulators of NRTN expression. Results: NRTN expression was significantly elevated in LSS patients versus controls at both transcript and protein levels (p < 0.05). NRTN levels positively correlated with pain intensity (VAS; ANOVA p = 0.032 for mRNA, p = 0.041 for protein). Multivariate regression identified BMI (β = 0.50, p = 0.015) and diabetes (β = 0.39, p = 0.017) as independent predictors of increased NRTN expression. Alcohol use also showed a positive association (p = 0.046), while smoking showed no significant independent effect. Conclusions: Neurturin is upregulated in ligamentum flavum tissue from LSS patients and correlates with pain severity and metabolic risk factors. These findings suggest NRTN as a potential biomarker and therapeutic target in degenerative spine disease. Further longitudinal and mechanistic studies are warranted to elucidate its role in chronic pain and neuroinflammation.

Degenerative lumbosacral spinal stenosis (DLSS) is a progressive condition characterized by narrowing of the spinal canal and subsequent neural compression, often leading to chronic pain and disability. Neurotrophins, particularly neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4), play essential roles in maintaining neuronal integrity and modulating nociceptive signaling; however, their involvement in DLSS and potential modulation by systemic and behavioral factors remain poorly understood. This study evaluated NT-3 and NT-4 expression in ligamentum flavum (LF) tissue from 96 patients undergoing surgical decompression for DLSS and compared the results to 85 postmortem control samples. Quantitative analyses were performed using RT-qPCR, ELISA, and immunohistochemistry. NT-3 transcript levels were markedly elevated in stenotic LF samples (fold change: 9.12 ± 0.56; p < 0.05), while NT-4 mRNA expression was significantly reduced (fold change: 0.33 ± 0.07; p < 0.05). At the protein level, both NT-3 (134 ± 5.78 pg/mL) and NT-4 (316.77 ± 8.19 pg/mL) concentrations were significantly increased compared to controls (p < 0.05). Although neurotrophin levels did not correlate directly with pain intensity or morphological severity, elevated NT-3 and NT-4 protein levels were significantly associated with obesity, diabetes, alcohol consumption, and tobacco use (p < 0.05). These findings demonstrate that NT-3 and NT-4 are differentially expressed in the ligamentum flavum of patients with DLSS and are influenced by systemic metabolic disturbances and lifestyle factors, suggesting their potential as biomarkers or therapeutic targets in degenerative spinal disease.