Composition-function relationships during IL-1-induced cartilage degradation and recovery

SummaryObjectiveTo examine the relationships between biochemical composition and mechanical properties of articular cartilage explants during interleukin-1 (IL-1)-induced degradation and post-exposure recovery.DesignBovine articular cartilage explants were cultured for up to 32 days with or without 20 ng/mL IL-1. The dynamic shear modulus |G*dyn| and equilibrium and dynamic unconfined compression moduli (Eequil and |E*dyn|) were measured at intervals throughout the culture period. In a subsequent recovery study, explants were cultured for 4 days with or without 20 ng/mL IL-1 and for an additional 16 days in control media. The dynamic moduli |E*dyn| and |G*dyn| were measured at intervals during degeneration and recovery. Conditioned media and explant digests were assayed for sulfated glycosaminoglycans (sGAG) and collagen content.ResultsContinuous IL-1 stimulation triggered progressive decreases in Eequil, |E*dyn|, and |G*dyn| concomitant with the sequential release of sGAG and collagen from the explants. Brief IL-1 exposure resulted in a short release of sGAG but not collagen, followed by a gradual and incomplete repopulation of sGAG. The temporary sGAG depletion was associated with decreases in both |E*dyn| and |G*dyn| which also recovered after removal of IL-1. During IL-1-induced degradation and post-exposure recovery, explant mechanical properties correlated well with tissue sGAG concentration.ConclusionsAs previously shown for developing cartilages and engineered cartilage constructs, cytokine-induced changes in sGAG concentration (i.e., fixed charge density) are coincident with changes in compressive and shear properties of articular cartilage. Further, recovery of cartilage mechanical properties can be achieved by relief from proinflammatory stimuli and subsequent restoration of tissue sGAG concentration.