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Proteomics of Knee Osteoarthritis
MRL/MpJ (super healers) mice have a unique ability to repair wounds and are protected from cartilage degradation subsequent to joint trauma. The hypothesis is that in response to injury, MRL/MpJ mice synthesize proteins that (1) protect the joint from cartilage degradation and/or (2) promote cartilage regeneration. The PIs propose to generate an atlas of the injury-activated proteome in mouse models with varying susceptibility to posttraumatic osteoarthritis (PTOA): (1) C57BL/6; (2) C57BL/6 treated with streptozotocin (STZ), a model of type 1 diabetes; (3) MRL/MpJ (super healers); and (4) STR/ort (spontaneous OA). By conducting comparative proteomics of injured and uninjured joints, the PIs will identify novel protein candidates for further exploration as potential therapies for treating injured joints. The projects specific aims are (1) application of in vivo metabolic labeling to quantify and characterize de novo protein synthesis, cellular proliferation, and mineral apposition in injured joints of mice with varying susceptibility to PTOA and (2) identification of newly synthesized RNA and proteins in the articular cartilage and immune cells of injured knees using a liquid sample interface for the AMS instrument in combination with liquid chromatography-mass spectrometry (LC-MS).
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