Aggrecan and small leucine-rich proteoglycan fragments correlate with Toll-like receptor-2 mediated inflammation in painful degenerative disc disease

Background: Painful intervertebral disc degeneration is a leading cause of chronic low back pain. Proteolytic cleavage fragments of extracellular matrix components, particularly aggrecan and small leucine-rich proteoglycans (SLRPs), may act as endogenous danger signals activating inflammatory pathways. To determine whether proteolytic fragments of aggrecan and SLRPs correlate with disc degeneration severity and Toll-like receptor-2 (TLR-2) mediated inflammation. Methods: Human disc tissues were analysed from 20 non-degenerated cadaveric controls (Thompson Grades 1-2) and 35 patients with painful degeneration (Pfirrmann Grades 3-5). Western blotting assessed fragmentation of aggrecan and SLRPs (decorin, biglycan, lumican, fibromodulin, chondroadherin). Immunofluorescence localized these molecules in disc sections. Disc cells were cultured under four conditions: unstimulated controls, TLR-2 agonist Pam2CSK4-stimulated controls, cells extracted from degenerated discs, and those treated with the TLR-2 antagonist MMG-11. Cytokine profiles were determined using antibody array. Results: < 0.001), further upregulated by Pam2CSK4 and attenuated by MMG-11. Cytokine analysis revealed marked pro-inflammatory shifts in patient discs (interleukin [IL]-6 ↑1.37×, IL-8 ↑1.30×, IL-1β ↑1.25×), while control discs exhibited an anabolic profile with elevated expressions of growth factors (TGF-β, EGF, VEGF). Conclusions: Aggrecan and SLRP fragments were observed alongside TLR-2 mediated inflammatory responses in advanced disc degeneration, suggesting a potential association with tissue catabolism. Targeting TLR-2 signaling may warrant further investigations as a potential therapeutic strategy for painful disc disease.