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

Abstract

Objective: To examine the relationships between biochemical composition and mechanical properties of articular cartilage explants during interleukin-1 (IL-1)-induced degradation and post-exposure recovery. Design: Bovine articular cartilage explants were cultured for up to 32 days with or without 20 ng/mL interleukin-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 20ng/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. Results: Continuous 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. Conclusions: As 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.

Meniscus is more susceptible than cartilage to catabolic and anti-anabolic effects of adipokines

“…Although the patterns of catabolism induced by adipokines (primarily resistin) and IL-1 are similar, further studies are required to determine the extent to which common pathways are involved in the response, an issue with implications for potential pharmacologic interventions to address early obesity- or injury-related degeneration. It should be noted that we used media including high glucose and insulin to ensure high metabolic activity [39] and for consistency with previous studies examining IL-1 effects on these tissues [36, 38]. Like cytokines such as IL-1 and TNF-α [40], some adipokines may regulate glucose metabolism in cartilaginous tissues, and the effects of glucose levels (both in vitro and in vivo) on adipokine-stimulated tissue catabolism should be examined.…”

“…Meniscus sGAG release was maximal immediately upon IL-1α treatment and steadily decreased until sGAG depletion [37] while cartilage exhibited more gradual sGAG release that peaked at about one week of treatment [38]. Although the patterns of catabolism induced by adipokines (primarily resistin) and IL-1 are similar, further studies are required to determine the extent to which common pathways are involved in the response, an issue with implications for potential pharmacologic interventions to address early obesity- or injury-related degeneration.…”

“…However, a greater susceptibility to inflammatory factors elevated as part of the injury response could contribute to earlier development of degeneration in meniscus than in articular cartilage. Meniscus has nearly an order of magnitude less proteoglycan content than cartilage, and small perturbations to the proteoglycan composition can induce larger relative loss of functional mechanical properties in meniscus than in cartilage [37, 38]. Following injury, the meniscus may be particularly susceptible to resistin-induced sGAG depletion even in the absence of macroscopic damage directly related to the trauma itself.…”

Regional variation in T1ρ and T2 times in osteoarthritic human menisci: correlation with mechanical properties and matrix composition

“…After unloading and recovery in PBS for 30 minutes, the samples were tested at room temperature in unconfined compression using an Instron 5848 MicroTester (Instron, Norwood, MA). Sequential compressive offsets of 5, 10, 15, and 20% were applied at 0.1%/s followed by stress relaxation for 20 minutes in order to obtain the equilibrium compressive modulus ( E eq ), which was determined via linear regression of the equilibrium stress vs. applied strain as described previously 30 . At the 10% offset, ±1.5% compressive strain was applied at 0.1Hz to determine the dynamic compressive modulus ( E *) based on Fast Fourier Transform analysis of the force data (MATLAB).…”

Osmotic Swelling Responses Are Conserved Across Cartilaginous Tissues With Varied Sulfated‐Glycosaminoglycan Contents

“…Interestingly, these apparent composition–function relationships were not maintained for enzymatically degraded cartilage explants, whose mechanical response to altered osmotic environments did not conform to the native tissue response, particularly the response of meniscus tissues with similar sGAG concentrations. While some studies have explored the particular effects of aging, degeneration, and repair in the structure–function relationships of a given tissue type (typically cartilage) and even suggested the interaction between sGAG and collagen in the compressive properties of cartilage, our study uncovered inter‐tissue relationships that, to our knowledge, have not been previously described. Furthermore, the trends reported here seem to hold for other musculoskeletal soft tissues outside the realm of the sGAG concentration spectrum tested, such as tendon (with collagen/dry mass values in the order of 100 µg/mg and sGAG/dry mass of approximately 1 µg/mg for flexor bovine tendons in 6‐month‐old calves) …”