The neuropeptide aCGRP impairs the chondrocyte response to mechanical load

Abstract

Mechanical loading can contribute to articular cartilage homeostasis due to its anabolic effects, for example the stimulation of glycosaminoglycan (GAG) synthesis. During degenerative joint diseases, such as osteoarthritis, the ability to respond adequately to mechanical stimulation may be compromised. The neuropeptide and pain mediator αCGRP has previously been associated with osteoarthritis and is typical for sensory nerve fibres, but chondrocytes also possess the receptors for αCGRP and have been shown to respond to treatment in vitro. Since it was reported that murine macrophages were more sensitive to αCGRP following stretching, we hypothesised that αCGRP may influence the response of chondrocytes to mechanical stimulation. Here, we employed our previously established model system using human articular chondrocytes to generate tissue-engineered cartilage to investigate the effect of the sensory neuropeptide αCGRP on the chondrocyte loading response. Following culture under chondrogenic conditions for 35 days, tissue-engineered cartilage was subjected to a three-hour episode of unconfined dynamic compression in the presence or absence of αCGRP. Addition of αCGRP did not exert obvious anti-chondrogenic effects, and typical mechano-response markers were not altered when mechanical loading was performed in the presence of αCGRP. GAG synthesis rates were stimulated by mechanical loading in the control group as expected, but this anabolic effect was prevented by the presence of αCGRP. Our results suggest that high levels of αCGRP may interfere with the mechano-adaptation of articular cartilage and this may have important implications for osteoarthritis pathology and therapy.