Enhancing Osteoclastic Resorption for the Prevention and Treatment of Heterotopic Ossification
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2012
- Accession Number
- ADA592935
Entities
People
- Kevin P. Mchugh
Organizations
- University of Florida