LYSYL OXIDASE AND MAILLARD REACTION-MEDIATED CROSS-LINKS IN AGING ANDOSTEOARTHRITIC RABBIT CARTILAGE

Alterations in the integrity of the extracellular matrix play an impor tant role in osteoarthritis. Matrix crosslinks in articular cartilage of the knee were studied in partially meniscectomized rabbits to compa re changes due to osteoarthritis with those occurring during aging. Py ridinoline, a lysyl oxidase-initiated crosslink, and pentosidine, a cr osslink formed by the Maillard/glycation reaction, were assayed separa tely on reverse-phase high performance liquid chromatography. A signif icant increase in the percentage of insoluble collagen was observed in normal 12-month-old rabbits compared with the levels in 3-month-old a nimals, whereas osteoarthritis was associated with a shift toward more soluble fractions. Total pyridinoline content did not change with age or osteoarthritis. Total pentosidine, however, increased significantl y with age but remained constant with osteoarthritis. Analysis of the distribution of crosslinks among solubility fractions indicated a sign ificant shift of pyridinoline from the pepsin-released fraction to the insoluble fraction with osteoarthritis, but no changes were observed with age. Pentosidine distribution shifted toward the pepsin-released fraction in osteoarthritis, with a shift toward the insoluble fraction with age. Because of the low levels of pentosidine present, its preci se location, whether collagenous or noncollagenous, remains unclear. H owever, since pentosidine represents a marker for the overall Maillard reaction, the results of our studies support a role for Maillard reac tion products in the aging of extracellular matrix. The shift of pento sidine toward more soluble fractions suggests the presence of matrix d egradation and repair in osteoarthritis.