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 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.
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).
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.
Neidlinger-Wilke C, University Ulm, Ulm, Germany
Wilke HJ (Prof), University Ulm, Ulm, Germany
Shenke-Layland K (Prof), University Tübingen, Tübingen, Germany