Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progression
Abstract Background Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage breakdown, subchondral bone remodeling, and inflammation. Mechanical stress, such as exercise, can influence OA progression, acting as either a therapeutic intervention or a risk factor dependi...
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BMC
2025-06-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-025-03589-6 |
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| author | Patrick Pann Paul Kalke Verena Maier Nicole Schäfer Hauke Clausen-Schaumann Arndt F. Schilling Susanne Grässel |
| author_facet | Patrick Pann Paul Kalke Verena Maier Nicole Schäfer Hauke Clausen-Schaumann Arndt F. Schilling Susanne Grässel |
| author_sort | Patrick Pann |
| collection | DOAJ |
| description | Abstract Background Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage breakdown, subchondral bone remodeling, and inflammation. Mechanical stress, such as exercise, can influence OA progression, acting as either a therapeutic intervention or a risk factor depending on intensity. The sensory neuropeptide αCGRP plays a role in modulating cartilage, bone, and inflammatory responses, making it a potential mediator of exercise effects on OA. This study investigated the impact of αCGRP deficiency and exercise intensity on OA progression in a post-traumatic murine model. Methods OA was induced in male αCGRP knockout (KO) and wild type (C57Bl/6J) mice via destabilization of the medial meniscus (DMM). Mice underwent moderate or intense treadmill exercise for up to 6 weeks (8 weeks post-surgery). Histological analyses were performed to assess cartilage degradation. Subchondral and metaphyseal bone morphology as well as cartilage stiffness were evaluated by nanoCT and atomic force microscopy (AFM), respectively. Serum inflammatory markers were analyzed using multiplex immunoassays. Results Serum levels of proinflammatory markers were elevated in αCGRP-deficient mice, particularly after intense exercise, independent of OA progression. DMM surgery induced significant cartilage degradation. Gross cartilage morphology was not influenced by exercise intensity or αCGRP deficiency, but αCGRP deficiency prevented articular cartilage extracellular matrix stiffening after DMM and intense exercise. Subchondral bone sclerosis was induced by αCGRP deficiency and DMM but mitigated by intense exercise. In metaphyseal bone, intense exercise induced trabecular loss in αCGRP-deficient mice. Conclusions This study highlights αCGRP as an intrinsic regulator of joint and bone responses to mechanical loading during OA. While cartilage degradation after DMM and treadmill exercise was unaffected by lack of αCGRP, its deficiency altered ECM stiffness, bone remodeling, and inflammatory responses. These findings position αCGRP as a critical regulator of joint homeostasis, particularly for bone health during running exercise and OA progression. |
| format | Article |
| id | doaj-art-63d1e9a65ebb4e2f9a03e6484a665897 |
| institution | OA Journals |
| issn | 1478-6362 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj-art-63d1e9a65ebb4e2f9a03e6484a6658972025-08-20T02:37:34ZengBMCArthritis Research & Therapy1478-63622025-06-0127111310.1186/s13075-025-03589-6Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progressionPatrick Pann0Paul Kalke1Verena Maier2Nicole Schäfer3Hauke Clausen-Schaumann4Arndt F. Schilling5Susanne Grässel6Dept. of Orthopaedic Surgery, Experimental Orthopaedics, Center for Medical Biotechnology, University of RegensburgDepartment of Trauma Surgery, Orthopedics and Plastic Surgery, University Medicine GöttingenCenter for Applied Tissue Engineering and Regenerative Medicine (CANTER), University of Applied Sciences MunichDept. of Orthopaedic Surgery, Experimental Orthopaedics, Center for Medical Biotechnology, University of RegensburgCenter for Applied Tissue Engineering and Regenerative Medicine (CANTER), University of Applied Sciences MunichDepartment of Trauma Surgery, Orthopedics and Plastic Surgery, University Medicine GöttingenDept. of Orthopaedic Surgery, Experimental Orthopaedics, Center for Medical Biotechnology, University of RegensburgAbstract Background Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage breakdown, subchondral bone remodeling, and inflammation. Mechanical stress, such as exercise, can influence OA progression, acting as either a therapeutic intervention or a risk factor depending on intensity. The sensory neuropeptide αCGRP plays a role in modulating cartilage, bone, and inflammatory responses, making it a potential mediator of exercise effects on OA. This study investigated the impact of αCGRP deficiency and exercise intensity on OA progression in a post-traumatic murine model. Methods OA was induced in male αCGRP knockout (KO) and wild type (C57Bl/6J) mice via destabilization of the medial meniscus (DMM). Mice underwent moderate or intense treadmill exercise for up to 6 weeks (8 weeks post-surgery). Histological analyses were performed to assess cartilage degradation. Subchondral and metaphyseal bone morphology as well as cartilage stiffness were evaluated by nanoCT and atomic force microscopy (AFM), respectively. Serum inflammatory markers were analyzed using multiplex immunoassays. Results Serum levels of proinflammatory markers were elevated in αCGRP-deficient mice, particularly after intense exercise, independent of OA progression. DMM surgery induced significant cartilage degradation. Gross cartilage morphology was not influenced by exercise intensity or αCGRP deficiency, but αCGRP deficiency prevented articular cartilage extracellular matrix stiffening after DMM and intense exercise. Subchondral bone sclerosis was induced by αCGRP deficiency and DMM but mitigated by intense exercise. In metaphyseal bone, intense exercise induced trabecular loss in αCGRP-deficient mice. Conclusions This study highlights αCGRP as an intrinsic regulator of joint and bone responses to mechanical loading during OA. While cartilage degradation after DMM and treadmill exercise was unaffected by lack of αCGRP, its deficiency altered ECM stiffness, bone remodeling, and inflammatory responses. These findings position αCGRP as a critical regulator of joint homeostasis, particularly for bone health during running exercise and OA progression.https://doi.org/10.1186/s13075-025-03589-6OsteoarthritisDestabilization of the medial meniscusAlpha-calcitonin gene-related peptideExerciseBoneCartilage |
| spellingShingle | Patrick Pann Paul Kalke Verena Maier Nicole Schäfer Hauke Clausen-Schaumann Arndt F. Schilling Susanne Grässel Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progression Arthritis Research & Therapy Osteoarthritis Destabilization of the medial meniscus Alpha-calcitonin gene-related peptide Exercise Bone Cartilage |
| title | Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progression |
| title_full | Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progression |
| title_fullStr | Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progression |
| title_full_unstemmed | Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progression |
| title_short | Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progression |
| title_sort | decoding the impact of exercise and αcgrp signaling on murine post traumatic osteoarthritis progression |
| topic | Osteoarthritis Destabilization of the medial meniscus Alpha-calcitonin gene-related peptide Exercise Bone Cartilage |
| url | https://doi.org/10.1186/s13075-025-03589-6 |
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