Kenny S. Jang
Shuying Yang
| Kenny S. Jang | Shuying Yang |
Kenny S. Jang1, Shuying Yang2, Shuting Yang2
1University of Pennsylvania, School of Dental Medicine; 2Basic & Translational Sciences, University of Pennsylvania, School of Dental Medicine
Introduction
Inflammatory osteolysis results in multiple diseases causing bone loss. Previous studies have shown that the conditional deletion of Intraflagellar Transport 80 gene (IFT80) leads to increased osteoclast differentiation. In this study, we analyzed the role of IFT80 in osteoclast differentiation and the potential use for overexpression of IFT80 as a treatment for inflammation induced osteolysis.
Methods
We used the lipopolysaccharide (LPS) induced mouse calvarial osteolytic bone defect model to compare bone healing between wild type and IFT80f/f; LysM-Cre. Our LPS model was divided into three groups including a control group left untreated, a group treated with Adenovirus-Green Fluorescent Protein (Ad-GFP), and a group treated with Ad-IFT80, showcasing the overexpression of IFT80. Mice were injected on their calvarial bone with LPS day 1 of birth and further treated with Ad-GFP or Ad-IFT80 on day 2. Within these groups, mice were divided into wild type and IFT80 knockout samples. Through genotyping and gel electrophoresis, we identified mice expressing IFT80 and Cre and harvested the calvarial bones for MicroCT analysis to acquire quantitative data of the size of bone healing and to develop 3D models of the samples. Frozen section cutting and Hematoxylin and Eosin Staining (H&E Staining) were performed for histological analysis.
Results
After LPS injection inducing inflammatory bone-loss, the overexpression of IFT80 via Ad-IFT80 increased healing on the calvarial bone in vitro. We anticipate that in vivo, overexpression of IFT80 will also induce healing as IFT80 inhibits osteoclastogenesis, resulting in the decrease of osteoclast formation. However, the IFT80 knockout model showed decrease in bone healing due to the increase of osteoclast differentiation.
Conclusion
Through this study, we have demonstrated that the deletion of IFT80 results in delayed healing of inflammatory osteolysis due to the increase of osteoclast differentiation and the overexpression of IFT80 is a possible treatment for inflammation-induced bone loss.