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

5/10/2013 1 Defective perilacunar remodeling by osteocytes in

• steonecrosis of the femoral

head

Faith Hall-Glenn, Aaron Fields, Ellen Liebenberg, Thomas Vail, Jeffrey Lotz and Tamara Alliston

Disclosures

• We have nothing to disclose

http://www.the-scientist.com/?articles.view/articleNo/27816/title/Full-Speed-Ahead/

Osteocytes are connected by the canalicular network

http://www.the-scientist.com/?articles.view/articleNo/27816/title/Full-Speed-Ahead/

Osteocyte perilacunar remodeling

Osteocytes remodel and resorb the bone matrix during lactation Qing et al., 2012 JBMR

5/10/2013 2

Matrix metalloproteinase 13 (MMP-13): a critical mediator of the canalicular network

WT MMP13-/- Tang et al., JBMR 2012

Does the disruption of osteocyte perilacunar remodeling contribute to

• steonecrosis?

https://www.meducation.net/encyclopedia/30642 Osteonecrosis

?

MMP-13

Glucocorticoids induce osteocyte apoptosis

Glucocorticoids Glucocorticoids

MMP-13 mediated Perilacunar Remodeling

?

Moutsatsou et al., 2012

Osteonecrosis patient sample preparation

Thomas Vail, Michael Ries, Kevin Bozic and Ellen Liebenberg

5/10/2013 3 Osteonecrosis patient sample preparation

Thomas Vail, Michael Ries, Kevin Bozic and Ellen Liebenberg

Osteonecrosis patient sample preparation

Thomas Vail, Michael Ries, Kevin Bozic and Ellen Liebenberg

Osteonecrosis patient sample preparation

Thomas Vail, Michael Ries, Kevin Bozic and Ellen Liebenberg

The osteocyte network is disrupted in osteonecrosis

5/10/2013 4 MMP-13 is decreased in

• steonecrotic lesions

Mouse model for studying

• steonecrosis progression

Vehicle Dexamethasone 0.01mg/ml

*

4x

Yang et al., J Ortho Res 2009

The canalicular network is disrupted by glucocorticoid treatment in mice

Vehicle Dexamethasone

GCs treated mice exhibit decreased MMP-13 expression

1 week GC treatment N=8; *** p=0.007183 Wilcoxen signed-rank test Femoral trabecular bone

5/10/2013 5 Glucocorticoids repress MMP-13 in cultured osteocytes

24 hour Dexamethasone treatment Student’s t test *p-value= 0.000437

Summary

Defective osteocyte remodeling MMP-13 Osteonecrosis Glucocorticoids Glucocorticoids Disruption

• f the canalicular network

Acknowledgements

Tamara Alliston, PhD Jeffrey Lotz, PhD Aaron Fields, PhD Ellen Liebenberg, MS Dezba Coughlin, PhD Thomas Vail, MD Michael Ries, MD Kevin Bozic, MD Funding Sources: Generous seed funding gifts from individual family and the UNCF/Merck Postdoctoral fellowship Department of Orthopaedic Surgery