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bioRxiv · 10.1101/871350

Overexpression Of Mig-6 In Limb Mesenchyme Leads To Accelerated Osteoarthritis In Mice

Rodrigues Bellini, M.·Pest, M. A.·Jeong, J.-W.·Beier, F.
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Abstract

BackgroundMitogen-inducible gene 6 (Mig-6) is a tumour suppressor gene that is also associated with the development of osteoarthritis (OA)-like disorder. Recent evidence from our lab and others showed that cartilage-specific Mig-6 knockout (KO) mice develop chondro-osseous nodules, along with increased articular cartilage thickness and enhanced EGFR signaling in the articular cartilage. Here, we evaluate the phenotype of mice with skeletal-specific overexpression of Mig-6. MethodsSynovial joint tissues of the knee were assessed in 12 and 36 weeks-old skeleton-specific Mig-6 overexpressing (Mig-6over/over) and control animals using histological stains, immunohistochemistry, semi-quantitative OARSI scoring, and microCT for skeletal morphometry. Measurement of articular cartilage and subchondral bone thickness were also performed using histomorphometry. ResultsOur results show only subtle developmental effects of Mig-6 overexpression. However, male Mig-6over/over mice show accelerated cartilage degeneration at 36 weeks of age, in both medial and lateral compartments of the knee. Immunohistochemistry for SOX9 and PRG4 showed decreased staining in Mig-6over/over mice relative to controls, providing potential molecular mechanisms for the observed effects. ConclusionOverexpression of Mig-6 in articular cartilage causes no major developmental phenotype but results in accelerated development of OA during aging. These data demonstrate that precise regulation of the Mig-6/EGFR pathway is critical for joint homeostasis.

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Rodrigues Bellini, M., Pest, M. A., Jeong, J.-W., Beier, F.. 2019-12-10. Overexpression Of Mig-6 In Limb Mesenchyme Leads To Accelerated Osteoarthritis In Mice. https://doi.org/10.1101/871350

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