The tissue renin-angiotensin system as new therapeutic target for treatment of disc degeneration (ProtectDisc)

German Spine Society
G Lang, J Pfannkuche, S Grad, Z Li, M Alini, D-C Kubosch, N Südkamp

Background

Low back pain is the leading cause of disability worldwide. Numerous patients with symptomatic intervertebral disc degeneration who failed conservative therapies and at the same time do not qualify for surgery still face the lack of a sufficient therapy that relieves pain while preserving motion. Recently, our group identified the expression of a tissue Renin-Angiotensin System (tRAS) in human intervertebral discs (IVD). This system contains two regulatory mechanisms: a pathological proinflammatory arm containing the Angiotensin Converting Enzyme (ACE)/Angiotensin II (AngII)/Angiotensin II receptor type 1 (AGTR1) axis and a protective anti-inflammatory arm containing the Angiotensin II receptor type 2 (AGTR2)/Ang1-7/MasReceptor axis. In our previous study, the expression of the pathologic arm was correlated with the extent of inflammation and tissue degeneration, indicating an involvement of this system in disc degeneration. 


Goal

The present study proposes to investigate the functional characteristics of the regulatory pathways and the therapeutic relevance of tRAS modulation in disc degeneration. Specifically, we aim to investigate the impact of pathologic tRAS arm inhibition and protective tRAS arm stimulation on inflammation and degeneration. Further, the impact of varying local Angiotensin II concentrations will be examined on human IVD cells. 

  • Publication

    Li Z, Wystrach L, Bernstein A, Grad S, Alini M, Richards RG, Kubosch D, Südkamp N, Izadpanah K, Kubosch EJ, Lang G. The tissue-renin-angiotensin-system of the human intervertebral disc. Eur Cell Mater. 2020;40:115-32

    Saravi B, Li Z, Pfannkuche J, Wystrach L, Häckel S, Albers CE, Grad S, Alini M, Richards RG, Lang C, Südkamp N, Schmal H, Lang G. Angiotensin II type 1 receptor antagonist Losartan inhibits TNF-α-induced inflammation and degeneration processes in human nucleus pulposus cells. Applied Sciences. 2021;11(1):417 https://doi.org/10.3390/app11010417

    Saravi B, Lang G, Grad S, Alini M, Richards RG, Schmal H, Südkamp N, Li Z. A proinflammatory, degenerative organ culture model to simulate early-stage intervertebral disc disease. JoVE. 2021(168):e62100. https://www.doi.org/10.3791/62100

  • Presentation

    Pfannkuche JJ, Li Z, Grad S, Alini M, Häckel S, Südkamp N, Schmal H, Lang G. Anti-inflammatory effects of Losartan in human nucleus pulposus cells.  2020 Eurospine virtual (poster)

    Wystrach L, Pfannkuche J, Li Z, Grad S, Kubosch DC, Schmal H, Alini M, Lang G. Die protektive Wirkung von Losartan auf humane Nucleus Pulposus Zellen. 
    Z Orthop Unfall. 2020;158(S01):S89-S90 (DKOU congress called off / abstract published, oral)

     
  • Partner

    Gernot Lang, University of Freiburg, Germany

    David-Christopher Kubosch, University of Freiburg, Germany

    Norbert Südkamp, University of Freiburg, Germany

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