PTHrP to Prevent Curve Progression in a Novel Murine Model of Early Onset Scoliosis

Michael B. Sullivan1,3, Ali Esmaeel1,3,Marco Kneifel4, Jean A. Ouellet1,3, Neil Saran1,3,, Janet E. Henderson1,2,3

1McGill University Department of Surgery, Montreal, Quebec, H3G 1A4, Canada; 2 McGill University Department of Medicine, Montreal, Quebec, H3G 1A4, Canada; 3 Research Institute of the McGill University Health Centre, Montreal, Quebec, H3G 1A4, Canada; 4University of British Columbia, Faculty of Engineering, Vancouver, British Columbia, V6T 1Z4, Canada

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Summary
Little is known about the pathogenesis of scoliosis, which is a three dimensional deformity of the spine. Mice deficient in FGF receptor 3 (FGFR3) signaling exhibit spine curvature at one month. It is hypothesized that the progressive curvature throughout life is caused in part by excessive bone cell apoptosis. A nuclear targeting sequence (NTS) in the mid-region of parathyroid hormone related protein (PTHrP) has been shown to prevent apoptosis in bone cells. Pellets (Innovative Research of America) containing NTS peptide, released to maintain a therapeutic dose for 60 days, are implanted in the concave aspect of the spines of 8 week old mice. Spine architecture and composition are evaluated by Xray, micro CT and histology.

 

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