Further study of these responses to determine their usefulness as markers of HIV-1 exposure as well as their protective potential is warranted. Risk factors for OA include age, sex, joint injury, obesity, and mechanical stresses. In addition, predisposition to OA has a considerable genetic component and it has been proposed that OA can be viewed as a continuum resulting from the interaction between genetics affecting cartilage extracellular matrix composition and joint shape and sensitivity to the other factors mentioned. Major efforts are made to identify loci associated with OA susceptibility to elucidate underlying mechanisms. Treatment options to slow down or reverse the OA process are still very limited and at the time of diagnosis the damage is already irreversible. Together, this emphasizes the importance to increase insight into the disease process and to identify genes and pathways involved in development of OA. A way to achieve this is by investigating the pathophysiological processes in articular cartilage by means of gene expression analyses. Initially, expression profiles were established for cartilage from knee OA joints in comparison to healthy joints using only a limited number of genes. More recently, exploratory genome wide expression profiling has been performed for the intact cartilage of hip and knee OA joints of patients undergoing joint replacement surgery RO5185426 compared to non-OA joints either derived from autopsies or from neck of femur fractures. These studies showed that many genes involved in extracellular matrix production as well as genes involved in ECM degradation or in inflammation were changed. Together, this resulted in significant enrichment for genes involved in skeletal development and response to external stimuli. Although studies that compare healthy cartilage with the preserved cartilage of joints from OA patients are very useful to acquire insight into the pathogenetic differences, the findings are likely biased by confounding factors such as innate differences, age, and stratification by joint. Moreover, due to the study design distinction between age-related changes and early or late changes of OA pathophysiology is hampered. One of the characteristics of OA is focal loss of articular cartilage, resulting in areas of degradation as well as areas with a relative preservation of cartilage thickness and appearance in the joint. Insight into gene expression specific for the focal areas of cartilage degradation compared to those in preserved areas can provide clues towards dynamic changes of genes and pathways involved in OA pathophysiology independent of confounding factors such as age. Gene expression profiles of cartilage from OA affected and macroscopically preserved areas of the same joint have been determined before, however, in most of these studies limited numbers of donors were included.