Doctoral defence: Taavi Torga "Association of molecular markers CILP-2, DDR2 and C2C with the severity of tissue damage in knee osteoarthritis"

On 5 September at 14:00 Taavi Torga will defend his thesis "Association of molecular markers CILP-2, DDR2 and C2C with the severity of tissue damage in knee osteoarthritis".

Supervisors:
Professor Andres Arend, University of Tartu
Associate Professor Siim Suutre, University of Tartu
Professor Kalle Kisand, University of Tartu
Associate Professor Marina Aunapuu, University of Tartu

Opponent:
Associate Professor Valērija Groma, Rīga Stradiņš University (Latvia)

Summary:

Osteoarthritis (OA) is the most common chronic joint disease, impacting millions globally, with the knee being the most commonly affected. Traditionally viewed as a “wear and tear” condition, OA is now recognized to originate from molecular changes that affect all joint tissues, including cartilage, bone, synovium, menisci, and ligaments. These molecular changes occur well before clinical symptoms become apparent. Consequently, molecular markers that can reflect changes during OA pathogenesis and potentially aid in early detection or serve as targets for disease-modifying therapy are crucial in OA research.

This study focused on the following putative OA markers: CILP-2 (cartilage intermediate layer protein 2), DDR2 (Discoidin Domain Receptor 2) and C2C (collagen type-II C-terminal cleavage neoepitope). We evaluated the expression of these biomarkers in cartilage samples obtained from OA patients who underwent total knee replacement. We assessed the local cartilage pathology and the extent of macroscopic damage using the OARSI OA Cartilage Histopathology Assessment System and compared the damage levels with the expression of biomarkers. In a separate methodological study, we identified the most suitable antigen retrieval method for CILP-2 immunohistochemistry.

Our findings indicate that CILP-2 and C2C are promising biomarkers for assessing knee OA severity. When comparing CILP-2 with DDR2, we found that while CILP-2 correlated with the several indicators of articular cartilage damage, DDR2 showed only a weak association. Thus, CILP-2 may be considered a superior OA marker compared to DDR2 based on our study. The C2C immunohistochemical study, using the antibodies applied in urine C2C ELISA assays, revealed a correlation of tissue-level expression and cartilage damage. Therefore, C2C can be considered a reliable OA marker, with urine assays detected C2C levels potentially reflecting the tissue-level changes.

You can watch the defence via Teams.