A Non -invasive Assay of Matrix Metalloproteinase Induced Musculoskeletal Syndrome in Rats using High Resolution Magnetic Resonance Imaging.
Hajdu R, Keohane C, Jackson J, Kennan R, Liu H, Miller Mandala S, Williams D
Merck & Co. Inc
Matrix metalloproteinases (MMPs) are considered excellent targets for drug development for arthritis and cancer. The clinical utility of MMP inhibitors has been restricted by a musculoskeletal side effect observed in humans and animal models. The objective of this study was to use MRI to characterize pathologic changes in a rat model of MMPinduced musculoskeletal syndrome (MSS). MRI detected growth plate and synovial fluid increases well before clinical signs. Over time, the growth plate increased by 5-fold, in agreement with previous histologic studies. Synovial fluid accumulated supra-linearly by 12 fold and was closely correlated with onset of behavioral symptoms.