The involvement of interleukin-1 and interleukin-4 in the response of human annulus fibrosus cells to cyclic tensile strain: an altered mechanotransduction pathway with degeneration

• DOI: 10.1186/ar3229
• Publication Date: 2011-02-08T14:51:14Z
• Authors: Hamish TJ Gilbert; Judith A Hoyland; Anthony J Freemont; Sarah J Millward-...
• Keywords: Mechanotransduction; Strain (injury); Interleukin 1β; Degeneration (medical); Intervertebral Disc; Annulus (botany); Tensile strain

Recent evidence suggests that intervertebral disc (IVD) cells derived from degenerative tissue are unable to respond physiologically relevant mechanical stimuli in the 'normal' anabolic manner, but instead by increasing matrix catabolism. Understanding nature of biological processes which allow sense and (a process termed 'mechanotransduction') is important ascertain whether these signalling pathways differ with disease. The aim here was investigate involvement interleukin (IL)-1 IL-4 response annulus fibrosus (AF) nondegenerative cyclic tensile strain determine cytokine differed IVD degeneration.AF were isolated human IVDs, expanded monolayers cyclically strained presence or absence inhibitors IL-1 receptor antagonist (IL-1Ra) antibody (IL-4RAb) 10% at 1.0 Hz for 20 minutes using a Flexcell device. Total RNA extracted time points baseline control 1 24 hours poststimulation. Quantitative real-time polymerase chain reaction used analyse gene expression proteins (aggrecan type I collagen) enzymes (matrix metalloproteinase 3 (MMP3) disintegrin thrombospondin motif 4 (ADAMTS4)).Expression catabolic genes (MMP3 ADAMTS4) decreased AF 1.0-Hz stimulation, this decrease inhibited increased following pretreatment IL-1Ra IL-4RAb respectively. Treatment an identical stimulus (1.0-Hz) resulted reduced collagen), having no effect.Both involved strain. Interestingly, altered observed appears be independent either cytokine, suggesting alternative mechanotransduction pathway operation.