Evaluation of differences in expression pattern of three isoforms of the transforming growth factor beta in patients with lumbosacral stenosis

Cell Cycle. 2024 Mar;23(5):555-572. doi: 10.1080/15384101.2024.2345484. Epub 2024 May 2.

Abstract

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.

Keywords: Yellow ligamentum flavum; degenerative spinal stenosis; transforming growth factor beta.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Humans
  • Ligamentum Flavum / metabolism
  • Ligamentum Flavum / pathology
  • Lumbar Vertebrae / metabolism
  • Lumbar Vertebrae / pathology
  • Lumbosacral Region / pathology
  • Male
  • Middle Aged
  • Protein Isoforms* / genetics
  • Protein Isoforms* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spinal Stenosis* / metabolism
  • Spinal Stenosis* / pathology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta2 / genetics
  • Transforming Growth Factor beta2 / metabolism
  • Transforming Growth Factor beta3 / genetics
  • Transforming Growth Factor beta3 / metabolism

Substances

  • Protein Isoforms
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Transforming Growth Factor beta
  • RNA, Messenger
  • Transforming Growth Factor beta3

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.