Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis

Abstract

The reaction patterns of chondrocytes in osteoarthritis can be summarized in five categories: (1) proliferation and cell death (apoptosis); changes in (2) synthetic activity and (3) degradation; (4) phenotypic modulation of the articular chondrocytes; and (5) formation of osteophytes. In osteoarthritis, the primary responses are reinitiation of synthesis of cartilage macromolecules, the initiation of synthesis of types IIA and III procollagens as markers of a more primitive phenotype, and synthesis of active proteolytic enzymes. Reversion to a fibroblast-like phenotype, known as "dedifferentiation", does not appear to be an important component. Proliferation plays a role in forming characteristic chondrocyte clusters near the surface, while apoptosis probably occurs primarily in the calcified cartilage.

Figure 1

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.