25dkou252 10.3205/25dkou252 urn:nbn:de:0183-25dkou2525 Meeting Abstract Pann Pann Patrick P

Dept. of Orthopaedic Surgery, University Medical Center Regensburg (UKR), Regensburg, Deutschland

author Kalke Kalke Paul P

Department of Trauma Surgery, University Medicine Göttingen, Göttingen, Deutschland

author Maier Maier Verena V

Center for Applied Tissue Engineering and Regenerative Medicine (CANTER), University of Applied Sciences Munich, Munich, Deutschland

author Schäfer Schäfer Nicole N

Dept. of Orthopaedic Surgery, University Medical Center Regensburg (UKR), Regensburg, Deutschland

author Clausen-Schaumann Clausen-Schaumann Hauke H

Center for Applied Tissue Engineering and Regenerative Medicine (CANTER), University of Applied Sciences Munich, Munich, Deutschland

author Schilling Schilling Arndt A author Grässel Grässel Susanne S

Dept. of Orthopaedic Surgery, University Medical Center Regensburg (UKR), Regensburg, Deutschland

author German Medical Science GMS Publishing House

Düsseldorf

610 20251031 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0634 252 Deutsche Gesellschaft für Orthopädie und Unfallchirurgie Deutsche Gesellschaft für Orthopädie und Orthopädische Chirurgie Deutsche Gesellschaft für Unfallchirurgie Berufsverband für Orthopädie und Unfallchirurgie Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2025) Grundlagenforschung | Biomechanik 1 Berlin 20251028 20251031 AB36-4453 TextObjectives and questions: Osteoarthritis (OA) is a prevalent degenerative joint disease marked by cartilage deterioration, subchondral bone alterations, and inflammation. Mechanical stress through exercise has a dual role in OA, offering both therapeutic and harmful effects depending on the intensity. The sensory neuropeptide α-calcitonin gene-related peptide (αCGRP) is known to influence cartilage integrity, bone remodeling, and inflammatory responses, suggesting a role in exercise-related changes in OA. This study aimed to examine the interplay between αCGRP deficiency and exercise intensity in OA progression using a post-traumatic murine model.Material and methods: OA was induced in male αCGRP knockout (KO) and wild type (C57Bl/6J) mice via destabilization of the medial meniscus (DMM). Following surgery, mice were subjected to either moderate or high-intensity treadmill exercise for up to eight weeks. Histological assessments evaluated cartilage degradation. Osteophyte formation as well as subchondral and subarticular bone changes were analyzed using nanoCT. Cartilage stiffness was measured through atomic force microscopy (AFM), and serum inflammatory markers were quantified via multiplex immunoassays.Results: Proinflammatory serum markers were elevated in αCGRP knockout mice, particularly following high-intensity exercise, independent of OA progression. DMM surgery led to significant cartilage degradation. However, gross cartilage morphology was not influenced by exercise intensity or αCGRP deficiency. αCGRP deficiency inhibited the stiffening of the articular cartilage extracellular matrix after DMM and intense exercise. Subchondral bone sclerosis was more pronounced in αCGRP-deficient mice after DMM and moderate exercise, whereas intense exercise reduced these sclerotic changes. In contrast, αCGRP-deficient mice experienced trabecular bone loss in subarticular regions after intense exercise.Discussion and conclusions: Our findings highlight αCGRP as a modulator of joint and bone responses to mechanical loading in OA. While cartilage degradation was not influenced by αCGRP deficiency, changes in extracellular matrix stiffness, bone remodeling, and systemic inflammation were significantly affected. These results suggest that targeting αCGRP signaling may offer new avenues for managing mechanical stress-related joint degeneration in OA. 0 0 0 0