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The purpose of the study is to investigate protein and gene expression among damaged knee tissues. We will perform MRI's on subjects prior to total knee replacement to identify the location of bone marrow lesions. Connective tissues including tendon, ligament, and meniscus specimens normally discarded from total joint replacements will be used for live cell harvest, and protein and gene expression analyses of tissue or cultured cells.
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BACKGROUND AND SIGNIFICANCE:
Although the presence of bone marrow lesions (BML) on MRI is strongly associated with osteoarthritis (OA) progression and pain in some studies, the mechanism for this relation and the underlying pathology is not well established. The lack of knowledge on what these lesions constitute hampers their clinical utility both with regards to measurement and targeting for therapeutic intervention.
Our preliminary data has localized specific changes in bone mineralization, remodeling and defects within BML features that are adjacent to the subchondral plate. BMLs appear to be sclerotic compared to unaffected regions; however, the mineral density in these lesions is reduced and may render this area to be mechanically compromised, and thus susceptible to attrition. Limited histological analysis of BMLs reveal thrombi, diffuse fibrinoid necrosis and hyperplasia of blood vessel walls - all indicative of infarction-like pathology.
The aim of this research proposal is to create more specific targets and improve our understanding of the pathology in BMLs.
Specific Aim 1:
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