Lysozyme in calcifying tissues.

Lysozyme, present in several connective tissues, is synthesized in cartilage by chondrocytes and immediately secreted into the extracellular matrix, where it is bound in the territorial (lacunar) matrix and along collagen fibers. In the epiphyseal growth plate, lysozyme levels increase toward the cartilage-bone junction, but cartilage lysozyme seems to be bound or inactivated by an inhibitor. Parathyroid extract injections decrease bone lysozyme levels. Cartilage lysozyme levels are low in rickets, while vitamin D increases it in both cartilage and aorta, suggesting an association between lysozyme and the calcification process. Although it is cationic and forms salt-like complexes with cartilage proteoglycans and chondroitin sulfate in vitro, lysozyme does not seem to be bound to proteoglycans in the native tissue. Proteoglycans in cartilage exist in a monomeric and aggregated form. Aggregation occurs by an interaction of monomers with hyaluronic acid and spedific link proteins. Aggregated proteoglycans inhibit mineral accretion in vitro. Mammalian cartilage lysozyme but not hen egg white lysozyme seems to inactivate this inhibitory capacity of aggregated proteoglycans, which is probably due to an interaction with hyaluronic acid resulting in a disaggregation. Therefore, we hypothesize that cartilage lysozyme plays an important role in the regulation and initiation of cartilage calcification.