SUMMARY
Researchers in the School of Dentistry at UCLA have developed a new method to detect periodontitis at early onset.
BACKGROUND
Adult periodontitis is a severe infection of the gums that presents with chronic gum inflammation, connective tissue degradation and irreversible bone loss, which can cause tooth loss. The National Health and Nutrition Examination Survey revealed periodontitis is present in 46% of US adults, and 8.9% of the people have developed severe or aggressive periodontitis. The progression of periodontitis is initiated by the collagen degradation of gingival and periodontal ligament, followed by the formation of periodontal pocket and alveolar bone resorption. During disease progression, osteoclasts, which are specialized cells that can induce bone resorption, are recruited to the site of infection and secrete large amounts of the extracellular matrix degrading protease cathepsin K (CatK). CatK is a well-established marker of enriched osteoclast activity, and individuals presenting with periodontitis are well characterized to possess elevated levels of CatK in surrounding fluid, even at early stages of the disease. Current examination and diagnosis for periodontitis involve periodontal pocket depth charting and dental radiography, neither of which can detect the initial tissue degradation prior to the formation of periodontal pocket and alveolar bone resorption. Therefore, there is an unmet need for diagnostic tools for periodontitis at early stages.
INNOVATION
Researchers in the School of Dentistry at UCLA and Department of Chemistry at USC have developed a novel diagnostic probe to detect the early signs of periodontitis. A chemical compound called Osteoadsorptive Fluorogenic Substrate 3 (OFS-3) is used to detect CatK activity, an enzyme that degrades the bone collagen matrix. OFS-3 has been shown to detect CatK activity in the mouse periodontitis model as early as day 3 after induction in a site-specific manner. Notably, OFS-3 transmits consistent signal through overlining gum tissues, enabling easy detection of the probe without tissue removal. Therefore OFS-3 can significantly improve the early detection of periodontitis and contribute to early interventions.
POTENTIAL APPLICATIONS
- Detection of early signs of periodontitis.
- Detection of other diseases including but not limited to hypocalcemia, hypoparathyroidism, osteoporosis, osteoarthritis, rheumatoid arthritis, and certain cancers.
ADVANTAGES
- Can detect early stages of periodontitis.
- Strong and consistent signals through overlining soft tissues.
- Novel fluorescent moiety has better penetrance and brightness than previously described CatK probes.
DEVELOPMENT-TO-DATE
The method has been tested in animal models.
RELATED PAPERS
Richard, E.T.; Morinaga, K; Zheng, Y; Sundberg, O; Hokugo, A; Hui, K; Zhou, Y; Sasaki, H; Kashemirov, B.A.; Nishimura, I; McKenna, C.E., “Design and Synthesis of Cathepsin-K-Activated Osteoadsorptive Fluorogenic Sentinel (OFS) Probes for Detecting Early Osteoclastic Bone Resorption in a Multiple Myeloma Mouse Model,” Bioconjug Chem. 2021, doi: 10.1021/acs.bioconjchem.1c00036.