Mouse Model of Osteoarthritis: Over-Expression of Smurf2 in Cartilage to Induce Disease and Over-expression of Smurf1 as a Potential Therapeutic Strategy

We have generated col2-promoter-Smad ubiquitin regulatory factor2 (col2-Smurf2) transgenic mice which possess a loss of TGFß signaling and display each of above characteristics, thus displaying a phenotype more representative of the disease process.  Furthermore, the over-expression of Smurf2 in cartilage that has been induced in these mice correlates with the increased Smurf2 expression that is seen in osteoarthritic cartilage tissue harvested from patients undergoing total knee arthroplasty due to osteoarthritis.

This col2-Smurf2 mouse model may present a phenotype consistent with osteoarthritis because it mimics the Smurf2 expression profile that is seen in the human disease.  Other transgenic or knockout models of arthritis in the mouse have not been accepted as valid representation of osteoarthritis.  Examples include the human tumor necrosis factor alpha (TNFa) transgenic (which have over-expression of TNFa under the control of its endogenous promoter), the col2 promoter-dominant negative type I transforming growth factor beta receptor (col2-DNTGF-ß receptor) transgenic and the Smad3 knockouts.  These models all show some form of erosive arthritis that manifests early (within 2-4 months) but are missing one or more of the phenotypic characteristics of osteoarthritis such as gradual onset during senescence, osteophyte formation, or cartilage loss without inflammation.

URV Reference Number: 6-1297
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