Enhancing Osteoclastic Resorption for the Prevention and Treatment of Heterotopic Ossification
Annual rept. 1 Dec 2011-30 Nov 2012
FLORIDA UNIV GAINESVILLE
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Bone-resorbing osteoclasts normally resorb ectopic mineral in their innate immune role. Therefore, we hypothesize that blockade of osteoclastic bone resorption is required for heterotopic bone formation and that lifting repression will allow resorption of ectopic bone in heterotopic ossification. Purpose to test methods to enhance osteoclast activity to reduce HO. Scope This work will use a mouse model of HO to test two different mechanisms to enhance osteoclast formation and function. The first is treatment of HO mice with exogenous RANKL, the key osteoclast formation cytokine. A second approach is by antibody inhibition of OPG, the natural antagonist of RANKL. Results from the second approach will be tested in OPG knockout mice. Major findings We have established colonies of all mice required for the experiments. We have established the mouse model of HO and characterized it by histological and histochemical analysis, X-ray, and micro-CT imaging. In addition, using osteoclast cell culture, we have screened and identified the best candidate anti-OPG antibody for inhibition experiments. We ARE testing anti-OPG antibody treatment in the HO model.
- Medicine and Medical Research