5/10/2013 Disclosures We have nothing to disclose Defective - PowerPoint PPT Presentation

5/10/2013 Disclosures • We have nothing to disclose Defective perilacunar remodeling by osteocytes in osteonecrosis of the femoral head Faith Hall-Glenn, Aaron Fields, Ellen Liebenberg, Thomas Vail, Jeffrey Lotz and Tamara Alliston http://www.the-scientist.com/?articles.view/articleNo/27816/title/Full-Speed-Ahead/ Osteocytes are connected by the Osteocyte perilacunar remodeling canalicular network Osteocytes remodel and resorb the bone matrix during lactation Qing et al., 2012 JBMR http://www.the-scientist.com/?articles.view/articleNo/27816/title/Full-Speed-Ahead/ 1

5/10/2013 Matrix metalloproteinase 13 (MMP-13): a Does the disruption of osteocyte critical mediator of the canalicular perilacunar remodeling contribute to network osteonecrosis? Osteonecrosis WT MMP13-/- ? MMP-13 Tang et al., JBMR 2012 https://www.meducation.net/encyclopedia/30642 Glucocorticoids induce osteocyte Osteonecrosis patient sample apoptosis preparation Glucocorticoids Glucocorticoids ? MMP-13 mediated Perilacunar Remodeling Moutsatsou et al., 2012 Thomas Vail, Michael Ries, Kevin Bozic and Ellen Liebenberg 2

5/10/2013 Osteonecrosis patient sample Osteonecrosis patient sample preparation preparation Thomas Vail, Michael Ries, Kevin Bozic and Ellen Liebenberg Thomas Vail, Michael Ries, Kevin Bozic and Ellen Liebenberg The osteocyte network is disrupted Osteonecrosis patient sample in osteonecrosis preparation Thomas Vail, Michael Ries, Kevin Bozic and Ellen Liebenberg 3

5/10/2013 MMP-13 is decreased in Mouse model for studying osteonecrotic lesions osteonecrosis progression Vehicle Dexamethasone 0.01mg/ml * 4x Yang et al., J Ortho Res 2009 GCs treated mice exhibit decreased The canalicular network is disrupted MMP-13 expression by glucocorticoid treatment in mice Femoral trabecular bone 1 week GC treatment Vehicle Dexamethasone N=8; *** p=0.007183 Wilcoxen signed-rank test 4

5/10/2013 Glucocorticoids repress MMP-13 in Summary cultured osteocytes Glucocorticoids Glucocorticoids 24 hour Dexamethasone treatment MMP-13 Defective osteocyte remodeling Disruption of the canalicular network Osteonecrosis Student’s t test *p-value= 0.000437 Acknowledgements Department of Orthopaedic Surgery Tamara Alliston, PhD Thomas Vail, MD Jeffrey Lotz, PhD Michael Ries, MD Aaron Fields, PhD Kevin Bozic, MD Ellen Liebenberg, MS Dezba Coughlin, PhD Funding Sources: Generous seed funding gifts from individual family and the UNCF/Merck Postdoctoral fellowship 5