Chondrocyte response to injury. (a) Injury and response. Mechanical insult, joint instability and inflammatory (generally catabolic) or anabolic cytokines can cause matrix activation, cell proliferation, apoptosis and eventually matrix destruction. Proteoglycan fragments (PG) are lost from the matrix. (b) Phenotypic modulation. Chondrocyte activation can result in modulation of gene expression resulting in different patterns of protein synthesis characteristic of chondrocyte development, fibroblasts 'dedifferentiation', hypertrophy (as seen in the growth plate) or regeneration of mature cartilage.