VARIATION IN PROTEOGLYCAN METABOLISM BY ARTICULAR CHONDROCYTES IN DIFFERENT JOINT REGIONS IS DETERMINED BY POSTNATAL MECHANICAL LOADING

In this study we investigated the hypothesis that cartilage from defin ed regions of ovine stifle joints, which were subjected to differing m echanical stresses, contained phenotypically distinct chondrocyte popu lations. Chondrocyte phenotypes were identified by the relative biosyn thesis of the proteoglycans (PGs) aggrecan, biglycan and decorin. Arti cular cartilage (AC) from adult and neonatal ovine stifle joints were examined. Cells were cultured as both full-depth AC explants and in al ginate beads after their isolation from the AC matrix. When chondrocyt es from the various topographical regions of adult ovine knee joints w ere cultured as explants they demonstrated a consistent difference wit h regard to the metabolism of aggrecan and decorin. Significantly, thi s topographically-dependent phenotypic expression of PGs was preserved when the chondrocytes were cultured in alginate beads. In adult joint s, chondrocytes from the central region of the tibial plateau not cove red by the meniscus, which is subjected to high mechanical loads in-vi vo, synthesized less aggrecan but more decorin than cells from regions covered by the meniscus. When chondrocytes from identical AC regions of neonatal ovine joints were cultured as explants, no topographical d ifference in aggrecan nor decorin metabolism could be detected. The re sults of this study, in association with the existing literature, lead us to propose that post-natal mechanical loading of AC could select f or chondrocyte clones or induce a lasting modulation of chondrocyte ph enotypic expression in different joint regions. Such cellular changes could result in the synthesis of PG populations that confer properties to AC most suited to resist the variable mechanical stresses in the d ifferent joint regions. This study serves to emphasize the importance of using cartilage from identical joint areas when examining PG metabo lism by chondrocytes. Further investigation into the relationship betw een mechanical loading, regional chondrocyte phenotype selection and t he response of these cells to anabolic and catabolic factors may provi de important insights into the focal nature of AC degeneration in oste oarthritis.