Neoepitope peptides as biomarkers of early intervertebral disc degeneration (NeoDisc) (Z Li, M Alini, S Grad, M Peroglio)

Background

To date there is an unmet need for reliable, predictive, cost effective diagnostic and prognostic tools for spinal disorders related to intervertebral disc (IVD) herniation or degeneration. Investigation into early molecular changes using a reproducible ex vivo model for disc degeneration, will identify tissue failure at the cellular and extracellular matrix level before structural changes occur.

 

Aggrecan neoepitope IHC staining with MMPCC antibody. Bovine caudal IVDs collected at day 0, cultured under physiological loading (Phy) for 1 day (short term) or 8 days (long term), or one strike loading followed by physiological loading for 0 (short term) or 7 days (long term). Quantification of the optical density (OD)/area value. Mean+SEM, n=8, * p<0.05. Scale 200 µm

 

Goal

Aggrecan and collagen cleavage occur in IVD aging and degeneration. This project aims to evaluate the appearance of these neoepitope peptides in IVD degeneration induced by detrimental mechanical loading, which may be utilized as early diagnostic biomarkers for disc herniation.

 

Results

Degeneration in bovine caudal IVDs was induced with one strike loading at 50% of the disc height followed by 0 (short term) or 7 days (long term) of culture under physiological loading. The IVDs were fixed with formalin, embedded in paraffin, and sectioned with a microtome. The existence of MMP cleaved C-terminus (MMPCC) aggrecan neoepitope was revealed with immunohistochemistry staining. The one strike loading long term group showed a stronger MMPCC aggrecan neoepitope staining intensity in the NP area compared with the day 0 healthy control, physiological group, and one strike short term group (Figure).


  • 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.
  • Presentation
    Cui S, Li W, Teixeira G, Neidlinger-Wilke C, Wilke H-J, Richards RG, Alini M, Grad S, Li Z. Neoepitope peptides biomarker for different types of intervertebral disc degeneration.  2021 ORS virtual (oral)
     
  • Partner

    Neidlinger-Wilke C, University Ulm, Ulm, Germany

    Wilke HJ (Prof), University Ulm, Ulm, Germany

    Shenke-Layland K (Prof), University Tübingen, Tübingen, Germany

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