TISSUE MICROARRAY ANALYSIS OF OSTEOARTHRITIS SAMPLES REVEALS DIFFERING MOLECULAR MECHANISMS DEPENDANT ON SUBCHONDRAL TRABECULAR BONE CHARACTERISTICS. A Opest, TA Freeman, Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA
Osteoarthritis (OA) is a common musculoskeletal disease of aging with multiple etiologies. Mechanical loading of the joint is known to influence cartilage degeneration, subchondral bone formation and remodeling. Our lab previously investigated differences in trabecular bone remodeling and found two different pathologies. The first response to cartilage loss showed an increase bone volume/total volume (BV/TV) and the other showed a decrease or no change in BV/TV. Based on these findings, we hypothesized that these differences represent distinct OA subpopulations exhibiting different molecular pathologies. To further investigate this, we created a tissue microarray from OA joint tissue samples which were divided into two groups; one group exhibiting increased BV/TV and one group showing decreased or no change in BV/TV. The array included the following tissue types: lesion, non-lesion and peri-lesional cartilage and bone samples and a synovial sample. The tissue cores were attached to a slide and subjected to immunohistochemical staining for eight proteins known to be associated with cartilage and bone OA. Results of the immunostaining were
analyzed densitometrically to create a quantitative protein localization profile for the tissues of the osteoarthritic joint. The data was then subjected to statistical analysis, including correlation and principal component analysis, on both the total patient population and each separate group for each tissue type individually. Our results show significantly different protein localization and quantity between both tissue types and the two groups. Additionally, this analysis identifies a specific OA protein profile which may have implications for differentially identifying early and late disease protein patterns and differences between the two subgroups of subchondral bone remodeling. Our hope is that this data will lead to the identification of biomarkers and potential drug targets for OA.
|