Academic Journal
Cellular senescence links muscle atrophy and posttraumatic osteoarthritis after ACL injury.
| Τίτλος: | Cellular senescence links muscle atrophy and posttraumatic osteoarthritis after ACL injury. |
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| Συγγραφείς: | Keeble AR; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States.; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, Kentucky, United States.; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, United States., Owen AM; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States.; Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, Kentucky, United States., Gonzalez-Velez S; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States.; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, United States., Thomas NT; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States.; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, Kentucky, United States., Brightwell CR; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States.; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, Kentucky, United States., Balawender PJ; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States., O'Daniel MG; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States., Weiss HC; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States., Noehren H; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States., Thompson H; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States.; Department of Biomedical Engineering, College of Engineering, University of Kentucky, Lexington, Kentucky, United States., Zuluaga-Osorio KS; Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, Kentucky, United States., Bates ZT; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States., Gottlieb L; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States., Long DE; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States., Harrison DA; Department of Biology, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky, United States., Kern PA; Division of Endocrinology, Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, United States., Conley CE; Department of Orthopaedic Surgery and Sports Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, United States., Samaan MA; Department of Kinesiology and Health Promotion, College of Education, University of Kentucky, Lexington, Kentucky, United States., Duncan ST; Department of Orthopaedic Surgery and Sports Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, United States., Stone AV; Department of Orthopaedic Surgery and Sports Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, United States., Johnson DL; Department of Orthopaedic Surgery and Sports Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, United States., Wen Y; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States.; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, United States.; Division of Biomedical Informatics, Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, United States., Noehren B; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States.; Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, Kentucky, United States.; Department of Orthopaedic Surgery and Sports Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, United States., Dungan CM; Department of Health, Human Performance, and Recreation, College of Health and Human Sciences, Baylor University, Waco, Texas, United States., Fry CS; Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, United States.; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, Kentucky, United States. |
| Πηγή: | Function (Oxford, England) [Function (Oxf)] 2026 Aug 01; Vol. 7 (4), pp. e0172026. Date of Electronic Publication: 2026 Jun 25. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 101770668 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2633-8823 (Electronic) Linking ISSN: 26338823 NLM ISO Abbreviation: Function (Oxf) Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Oxford, UK] : Oxford University Press, [2020]- |
| Ιατρικοί όροι (MeSH): | Cellular Senescence*/drug effects , Cellular Senescence*/physiology , Anterior Cruciate Ligament Injuries*/complications , Anterior Cruciate Ligament Injuries*/pathology , Muscular Atrophy*/etiology , Muscular Atrophy*/pathology , Osteoarthritis, Knee*/etiology , Osteoarthritis, Knee*/pathology , Osteoarthritis*/etiology , Osteoarthritis*/pathology, Quercetin/pharmacology ; Macrophages/pathology ; Macrophages/metabolism ; Dasatinib/pharmacology ; Dasatinib/therapeutic use ; Senotherapeutics/pharmacology ; Muscle, Skeletal/pathology ; Animals ; Humans ; Male ; Female ; Disease Models, Animal ; Mice |
| Περίληψη: | Traumatic knee injury leads to posttraumatic osteoarthritis (PTOA) and significant skeletal muscle weakness, resulting in chronic disability. The current standard of care frequently fails to prevent musculoskeletal dysfunction, underscoring the need to identify therapeutic mechanisms of PTOA. Using an established preclinical anterior cruciate ligament (ACL) transection model of PTOA and leveraging an innovative SPiDER-senescence-associated β-galactosidase stain to discern senescent cells, we investigated cellular senescence at single-cell resolution and identified anti-inflammatory macrophages as a predominant contributor to the senescent cell burden in both muscle and knee joint after injury. Clearance of senescent cells using the senolytic dasatinib and quercetin (D + Q) mitigated injury-induced muscle atrophy and cartilage degradation, with greater senescent cell clearance within muscle compared with cartilage. We also provide clinical evidence of elevated senescent cell burden in the muscle of patients following ACL injury and with PTOA, which is obstinate to standard of care, highlighting cellular senescence as a strong therapeutic target to improve functional recovery after traumatic joint injury.NEW & NOTEWORTHY Posttraumatic osteoarthritis (PTOA) and disability are consequences of ACL injury, but the cellular effectors that facilitate this process are unknown. Our findings demonstrate increased senescent macrophage burden in the muscle and knee joint in a preclinical ACL injury model, as well as in patients who predict poor muscle quality and weakness. We provide evidence that treatment with senolytics is an effective strategy to improve tissue quality and function and mitigate PTOA severity. |
| Contributed Indexing: | Keywords: fibroadipogenic progenitor cells; muscle fibrosis; quadriceps; senolytic; skeletal muscle |
| Substance Nomenclature: | 9IKM0I5T1E (Quercetin) RBZ1571X5H (Dasatinib) 0 (Senotherapeutics) |
| Entry Date(s): | Date Created: 20260625 Date Completed: 20260721 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13387088 |
| DOI: | 10.1152/function.017.2026 |
| PMID: | 42348390 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2633-8823 |
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| DOI: | 10.1152/function.017.2026 |