Microenvironment regulation of extracellular signal–regulated kinase activity in chondrocytes: Effects of culture configuration, interleukin‐1, and compressive stress

Objective To compare extracellular signal–regulated kinase (ERK) activity in response to interleukin‐1 (IL‐1) in chondrocytes under various culture configurations designed for the study of cartilage biology and repair, and also in response to dynamic load for chondrocytes in cartilage. Methods Isolated bovine articular chondrocytes were maintained in serum‐supplemented medium under 4 culture configurations: high‐density monolayer, attached to a cut surface of cartilage, within tissue‐engineered constructs, or within intact cartilage explants. Samples were subjected to a change of medium with or without IL‐1. Cartilage explants were also subjected to dynamic compression. Results In chondrocyte monolayers, both basal and IL‐1–stimulated ERK activities were similarly elevated at 0.5 hours after medium change, diminishing by 74% after 16 hours. In contrast, chondrocytes in other culture configurations exhibited lower basal levels of ERK activity and a moderate activation of ERK in response to IL‐1 that was sustained over the 16‐hour treatment time. The dynamic component of loading of cartilage explants led to a 5‐fold activation of ERK, compared with free‐swelling controls, that was indistinguishable from the effects of IL‐1. Conclusion ERK signaling in response to IL‐1 in chondrocyte monolayers exhibited a pattern that was distinct from that in other culture systems, suggesting that the extracellular matrix plays an important regulatory role in modulating the response to extracellular stimuli. Since IL‐1 and dynamic loading have distinct effects on chondrocyte biosynthesis, signaling pathways other than ERK participate in the chondrocyte responses to these stimuli.