Title: The tissue-renin-angiotensin-system of the human intervertebral disc

Authors: Z Li, L Wystrach, A Bernstein, S Grad, M Alini, RG Richards, D Kubosch, N Südkamp, K Izadpanah, EJ Kubosch, G Lang

Address: Department of Orthopaedics and Trauma Surgery, Medical Centre, Faculty of Medicine, Albert Ludwig University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany

E-mail: Gernot.michael.lang at uniklinik-freiburg.de

Abstract: Symptomatic intervertebral disc (IVD) degeneration accounts for significant 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. The present study investigated the expression of tRAS in human IVDs, and the correlation between tRAS, inflammation and IVD degeneration.
Human IVD tissue was collected during spine surgery and distributed according to principal diagnosis. Gene expression of tRAS components, proinflammatory and catabolic markers in the IVD tissue was assessed. Hydroxyproline (OHP) and glycosaminoglycan (GAG) content in the IVD tissue were determined. Tissue distribution of tRAS components was investigated by immunohistochemistry.
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. 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). Within tRAS-positive samples, AGT, matrix-metalloproteinases 13 and 3, IL-1, IL-6 and IL-8 were more highly expressed in traumatic compared to degenerated IVDs. Total GAG/DNA content of non-tRAS expressing IVD tissue was significantly higher compared to tRAS positive tissue. Immunohistochemistry confirmed the presence of AngII in the human IVD.
The present study identified the existence of tRAS in the human IVD and suggested a correlation between tRAS expression, inflammation and ultimately IVD degeneration.

Key Words: Intervertebral disc, renin angiotensin system, degeneration, regeneration, spine, inflammation.

Publication date: October 2nd 2020

Article download: Pages 115-132 (PDF file)
DOI: 10.22203/eCM.v040a07