Development of an exosome-based diagnostic platform for periodontal disease and root resorption

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ABSTRACT / PROJECT SUMMARY Dysregulated bone or dentin resorption is associated with a host of oral diseases including periodontitis and external root resorption, to name a few. Currently, standard diagnosis of these conditions relies on radiographic findings or computed tomography (CT) scans. Nevertheless, these methods usually detect the problem at an advanced stage where significant tissue damage had occurred, oftentimes leading to tooth loss. Moreover, imaging techniques may not indicate if `clastic' cell activity is ongoing or historical. Exosomes are small vesicles of endosomal origin that are released by different cell types after fusion of multi-vesicular bodies with the plasma membrane. Due to their protein, lipid and nucleic acids contents, which closely reflect the nature and state of their parental cells, exosomes are considered an important source of information. Here we present preliminary data demonstrating that 1) there is a difference in composition of exosomes shed from clastic cells resorbing bone (osteoclasts) vs. clastic cells resorbing dentin (odontoclasts), and 2) exosomal proteins involved in clastic cell activity can be identified in gingival crevicular fluid (GCF) collected from resorbing teeth. Thus, we hypothesize that there is a difference in the biochemical composition of exosomes released during the processes of bone and dentin resorption that would allow for distinction between odontoclastic and osteoclastic function. We will test this hypothesis by pursuing the following two specific aims: 1) To Isolate and characterize exosomes derived from osteoclasts and odontoclasts in vitro, and 2) To establish the clinical feasibility of an exosome-based assay in the detection of oral conditions where upregulated bone or dentin resorption is present. In summary, the overall goal of this project is to optimize procedures for exosome analysis while at the same time testing the capability of oral-fluid derived exosomes to distinguish osteoclast-active sites from odontoclast-active sites in vivo. The study will provide a basis for the development of new, safer and less expensive tests to diagnose and monitor the progression of periodontal disease and dental root resorption.