Disturbed cartilage and joint homeostasis resulting from a loss of mitogen-inducible gene 6 in a mouse model of joint dysfunction.

摘要: Objective Mitogen-inducible gene 6 (MIG-6) regulates epidermal growth factor receptor (EGFR) signaling in synovial joint tissues. Whole-body knockout of the Mig6 mice has been shown to induce osteoarthritis and degeneration. To evaluate role chondrocytes this process, was conditionally deleted from Col2a1-expressing cell types cartilage mice. Methods Bone joints cartilage-specific Mig6-deleted (knockout [KO]) control littermates were compared. Histologic staining immunohistochemical analyses used pathology as well expression key extracellular matrix regulatory proteins. Calcified tissue assessed by micro–computed tomography (micro-CT) whole-skeleton staining. Results Formation long bones found be normal KO animals. Cartilage thickness proteoglycan articular knee 12-week-old increased compared controls, with higher cellularity throughout tissue. Radiopaque chondro-osseous nodules appeared knees animals 12 weeks age progressed calcified bone–like 36 age. Nodules also observed spine 36-week-old Erosion bone at ligament entheses evident age, both histologic micro-CT assessment. Conclusion MIG-6 is important for maintenance homeostasis. Dysregulation EGFR results anabolic activity cartilage, but erosion formation ectopic severely disturb physiology.