{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:26:46Z","timestamp":1791556006012,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2024,12,22]],"date-time":"2024-12-22T00:00:00Z","timestamp":1734825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Knee osteoarthritis contributes substantially to worldwide disability. Post\u2010traumatic osteoarthritis (PTOA) develops secondary to joint injury, such as ligament rupture, and there is increasing evidence suggesting a key role for inflammation in the aetiology of PTOA and associated functional deficits. Colony stimulating factor 1 receptor (CSF1\u2010R) has been implicated in the pathogenesis of musculoskeletal degeneration following anterior cruciate ligament (ACL) injury. We sought to assess the efficacy of CSF1\u2010R inhibition to mitigate muscle and joint pathology in a mouse model of PTOA. Four\u2010month\u2010old mice were randomized to receive a CSF1\u2010R inhibitor and studied for 7 or 28\u00a0days after joint injury. Additionally, we profiled synovial fluid samples for CSF1\u2010R from patients with injury to their ACL. Transcriptomic analysis of quadriceps muscle and articular cartilage in CSF1\u2010R inhibitor\u2010treated animals at 7\u00a0days after injury revealed elevated chondrocyte differentiation within articular cartilage and enhanced metabolic and contractile gene expression within skeletal muscle. At 28\u00a0days post\u2010injury, CSF1\u2010R inhibition attenuated PTOA severity and mitigated skeletal muscle atrophy. Patient synovial fluid CSF1\u2010R levels correlated with matrix metalloproteinase 13, a prognostic marker and molecular effector of PTOA. Our findings support an opportunity for CSF1\u2010R targeting to mitigate the severity of PTOA and muscle atrophy after joint injury.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16478-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Posttraumatic osteoarthritis (PTOA) of the knee commonly results from direct injury to the joint, which is characterized by pain, weakness, and disability.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Induction of colony stimulating factor one receptor (CSF1\u2010R) is positively associated with knee trauma severity, and the initial acute inflammatory state suppresses muscle recovery and degrades articular cartilage.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Skeletal muscle and articular cartilage transcriptomic response following direct joint injury in a murine model of PTOA is rescued by pharmacological inhibition of CSF1\u2010R.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>CSF1\u2010R inhibition mitigated skeletal muscle atrophy and attenuated PTOA severity and synovitis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Patient synovial fluid CSF1\u2010R levels correlated with matrix metalloproteinase 13, a prognostic marker and molecular effector of PTOA, offering further evidence for CSF1\u2010R as a therapeutic target across musculoskeletal tissues after injury.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp286815","type":"journal-article","created":{"date-parts":[[2024,12,22]],"date-time":"2024-12-22T04:18:50Z","timestamp":1734841130000},"page":"7549-7566","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["CSF1\u2010R inhibition attenuates posttraumatic osteoarthritis and quadriceps atrophy following ligament injury"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5895-4315","authenticated-orcid":false,"given":"Alexander R.","family":"Keeble","sequence":"first","affiliation":[{"name":"Center for Muscle Biology University of Kentucky  Lexington KY USA"},{"name":"Department of Physiology, College of Medicine University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4578-8463","authenticated-orcid":false,"given":"Nicholas T.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology University of Kentucky  Lexington KY USA"},{"name":"Department of Athletic Training and Clinical Nutrition, College of Health Sciences University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyton J.","family":"Balawender","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille R.","family":"Brightwell","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology University of Kentucky  Lexington KY USA"},{"name":"Department of Athletic Training and Clinical Nutrition, College of Health Sciences University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6442-8181","authenticated-orcid":false,"given":"Sara","family":"Gonzalez\u2010Velez","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology University of Kentucky  Lexington KY USA"},{"name":"Department of Physiology, College of Medicine University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline G.","family":"O'Daniel","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology University of Kentucky  Lexington KY 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