Immuno-stimulatory capacity of decorin in the rat tail intervertebral disc and the mechanical consequence of resultant inflammation

摘要

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. 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; TNF ) were quantified over 24 h. Whole rat tail IVD cultures (n = 50) were also treated with decorin (two concentrations: 0.5 and 5.0g/mL) with and without TAK-242 (via nucleus pulpous injection with a 33-gauge needle), and resultant mechanical properties were measured. 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). 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.