The tissue-renin-angiotensin-system in degenerated intervertebral disc

S Grad, Z Li

Background

Intervertebral disc (IVD) degeneration causes back pain which accounts for significant global socioeconomic burden. Recently, the expression of the tissue-Renin-Angiotensin-System (tRAS) in rat and bovine IVD was demonstrated. The major effector of tRAS is Angiotensin II (AngII), which participates in proinflammatory pathways.

 

Left: relative gene expression levels of tRAS factors classified by diagnosis. Right: relative gene expression levels of catabolic, anabolic and proinflammatory genes in human IVDs classified by tRAS expression

 

Goal

As inflammation contributes to IVD degeneration, the present study sought to investigate the expression of tRAS in the human IVD, and the correlation between tRAS, inflammation, and degeneration in human IVD tissue.

 

Results

Gene expression of tRAS components such as angiotensin-converting-enzyme (ACE), Ang II receptor type 2 (AGTR2), angiotensinogen (AGT), and cathepsin D (CTSD) was confirmed in human IVDs (Figure 11.9.7 left). IVD samples that expressed tRAS components (n=21) revealed significantly higher expression levels of interleukin 6 (IL-6), tumour necrosis factor α (TNF-α), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 and 5 compared to tRAS-negative samples (n=37) (Figure 11.9.7 right). Furthermore, within tRAS-positive samples, AGT, Matrix-Metalloproteinases 13 and 3, IL-1, IL-6, and IL-8 were expressed significantly more highly in traumatic compared to degenerated IVDs. Biochemical analysis of IVD tissue revealed significantly higher total GAG/DNA content of non-tRAS expressing IVD tissue compared to tRAS positive tissue. Immunohistochemistry confirmed the presence of AngII in the human IVD. This study identified the existence of tRAS in the human IVD and suggests a correlation between tRAS expression, inflammation, and ultimately IVD degeneration.

Fund:

German Spine Society, EUR 23'000, period: 01.01.2016-30.09.2019.

 

  • Publication

    Pfannkuche J-J, Guo W, Cui S, Ma J, Lang G, Peroglio M, Richards RG, Alini M, Grad S, Li Z. Intervertebral disc organ culture for the investigation of disc pathology and regeneration – benefits, limitations, and future directions of bioreactors. Connective Tissue Research 2019, 26(9):1-18.

    Saravi B, Li Z, Lang CN, Schmid B, Lang FK, Grad S, Alini M, Richards RG, Schmal H, Südkamp N, Lang GM. The tissue renin-angiotensin system and its role in the pathogenesis of major human diseases: Quo vadis? Cells. 2021;10(3):650. https://doi.org/10.3390/cells10030650

     
  • Presentation

    Pre-clinical testing of anti-inflammatory compounds in an intervertebral disc organ culture model, BioSpine, 2019 April 3-5, Rome, Italy – Zhen Li (oral)

    Preclinical Testing of Anti-Inflammatory Compounds Using a Whole Intervertebral Disc Organ Culture Model. Global Spine Congress, 2019 May 15-18, Toronto, Canada – Sibylle Grad (oral)

    The Tissue-Renin-Angiotensin-System of the Human Intervertebral Disc, ORS 2019, Austin, US – Gernot Lang (poster)

  • Partner

    Lang G (MD), Albert-Ludwigs-Universität Freiburg, Freiburg, Germany

    Südkamp N (Prof), Albert-Ludwigs-Universität Freiburg, Freiburg, Germany

Completed