Purpose: Determine whether decorin is immuno-stimulatory to rat tail IVD cells and to characterize the mechanical consequence of inflammation at the whole rat tail IVD level.
Methods: Cultured rat tail annulus fibrosus (AF) cells were exposed to decorin, a resident IVD small leucine-rich proteoglycan (SLRP), with and without the presence of a toll-like receptor (TLR) 4 inhibitor, TAK-242. Resultant expression of pro-inflammatory cytokine and chemokines (MCP-1; MIP-2; RANTES; IL-6; TNFα) were quantified over 24 h. Whole rat tail IVD cultures (n = 50) were also treated with decorin (two concentrations: 0.5 and 5.0 μg/mL) with and without TAK-242 (via nucleus pulpous injection with a 33-gauge needle), and resultant mechanical properties were measured.
Results: AF cells exposed to decorin showed significant increases in pro-inflammatory cytokine and chemokine production; this was significantly blunted with the presence of TAK-242. Whole IVDs injected with decorin showed a dose-dependent decrease in neutral zone and tensile stiffness and an increase in neutral zone size. When TAK-242 was injected into the IVD with the decorin, mechanical stiffness was preserved and not different from sham controls (injected with PBS).
Conclusion: AF cells are capable of detecting decorin and inducing inflammation. Decorin further resulted in a functional deterioration in IVD mechanical integrity. TAK- 242, a TLR4 inhibitor, blunted chemokine production at the cellular level and preserved mechanical stiffness in the whole IVD.
Keywords: Annulus fibrosus; Biomechanics; Inhibitor; Small leucine-rich proteoglycan; Toll-like receptor.