Molecular principles of induction and progression of osteoarthritis

From a morphological point of view, osteoarthritis is characterized by cont inuous loss of the cartilage matrix, an increased density of the subchondra l bone, and partial involvement of the synovial compartment Research activi ties are focussing on gene expression and gene regulation in normal and ost eoarthritic cartilage to develop prognostic markers and new therapeutic str ategies. In general, chondrocytes from normal adult articular cartilage show low met abolic activity However in osteoarthritis, activation and differentiation o f chondrocytes occur. Activation involves anabolic pathways such as an enha nced expression of type II collagen as well as catabolic patterns such as t he increased expression of matrix metalloproteinases. These metabolic pathw ays are unbalanced,leading to insufficient cartilage architecture,unable to meet the requirements for mechanical stability and load compensation. In osteoarthritis, chondrocyte differentiation is characterized by the expr ession of type X collagen. Further differentiation stages have been observe d as shown for the expression of osteocalcin,osteopontin, or alkaline phosp hatase in articular cartilage. This altered expression pattern of chondrocy tes is likely to influence the biochemical and biomechanical properties of the cartilage matrix. In conclusion,new analytic and comparative methods to analyze gene and prot ein expression offer powerful tools to elucidate candidate genes in osteoar thritis. Detailed information on the regulatory pathways will be the basis for modulation of chondrocyte behavior and,therefore, may lead to new thera peutic approaches in the treatment of osteoarthritis.