{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:58:24Z","timestamp":1791244704440,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000894","name":"Spinal Muscular Atrophy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000894","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skeletal muscle mass maintenance involves coordination of myofibers with mononuclear cell populations, including satellite cells, resident macrophages and fibro\u2010adipogenic progenitors (FAPs). FAPs, identified by surface expression of PDGFR\u03b1, are important contributors to muscle homeostasis, as genetic ablation of FAPs induces rapid muscle atrophy. However, mechanisms underlying this response remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We utilized tamoxifen\u2010inducible FAP specific diptheria toxin (DTA) mice (\n                      <jats:italic>Pdgfra<\/jats:italic>\n                      <jats:sup>Cre\u2010ERT2\/+;<\/jats:sup>\n                      <jats:italic>Rosa26<\/jats:italic>\n                      <jats:sup>^DTA\/+<\/jats:sup>\n                      ) to evaluate consequences of FAP deletion, measuring body and muscle mass, and isolated function on the extensor digitorum longus (EDL) and soleus (SOL). Neuromuscular junction (NMJ) patency was assessed via whole\u2010mount staining, nerve vs. direct muscle stimulated function, and denervation\u2010responsive expression targeting AchR\u03b1\/\u03b2\/\u03b3. Immunofluorescence of muscle sections was used to investigate cellular and morphological changes. RT\u2010qPCR measured expression of atrogenes, inflammatory chemokines\/cytokines, and growth factors in tibialis anterior (TA) muscles. To modulate the immune response, mice were subjected to immune cell depletion, pharmacological Cxcr2 inhibition, or treatment with the anti\u2010inflammatory steroid Vamorolone (VBP15).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following tamoxifen administration, FAP density decreased 90%, coupled with a 30% loss of lean mass (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Isolated contractile measurements showed that FAP\u2010deleted muscles exhibited 25% reductions in maximal tetanic force in the EDL and SOL, while specific force and vulnerability to contractile damage remained unchanged. Whole\u2010mount staining revealed preserved NMJ structural integrity, and functional testing showed no differences between nerve and direct muscle stimulation. RT\u2010qPCR showed no change in genes encoding AchR subunits. Longitudinal body composition tracking revealed that FAP\u2010deletion\u2010induced muscle and fat loss occurred during tamoxifen administration and coincided with a 10\u2010fold increase in the infiltration of macrophages and neutrophils. Robust 10\u2010 to 150\u2010fold increases (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) in chemokine transcript levels was observed soon after FAP deletion but preceded atrogene upregulation (\n                      <jats:italic>Trim63, Fbxo32, Sqstm1, Ulk1<\/jats:italic>\n                      ).\n                      <jats:italic>Ccl2<\/jats:italic>\n                      increased ~80\u2010fold,\n                      <jats:italic>Ccl12<\/jats:italic>\n                      \u2009~\u200980\u2010fold,\n                      <jats:italic>Cxcl1<\/jats:italic>\n                      \u2009~\u200950\u2010fold, and\n                      <jats:italic>Cxcl2<\/jats:italic>\n                      \u2009~\u200950\u2010fold. While immune cell depletion exacerbated muscle atrophy by worsening mass loss and further increasing atrogene expression 5\u2010fold, Cxcr2 inhibition or VBP15 treatment restored muscle mass by 15% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). VBP15 treatment also resulted in a 50% reduction in atrogene expression and a 70% reduction in\n                      <jats:italic>Cxcl1\/2<\/jats:italic>\n                      expression levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings demonstrate that FAP deletion results in simple muscle atrophy without affecting muscular contractile properties and NMJ function. The atrophy induced by the loss of FAPs occurs through an inflammation\u2010mediated, Cxcl1\/2\u2010dependent mechanism, caused by the response to FAP cell death potentially coupled with the absence of FAP actions on the inflammatory environment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70393","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:58:42Z","timestamp":1790747922000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibro\u2010Adipogenic Progenitor Ablation Triggers Muscle Atrophy Through Cell Death\u2010Induced Inflammation"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7418-0030","authenticated-orcid":false,"given":"Yangyi E.","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Applied Physiology and Kinesiology, College of Health and Human Performance University of Florida  Gainesville Florida USA"},{"name":"Myology Institute University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4993-9038","authenticated-orcid":false,"given":"Young il","family":"Lee","sequence":"additional","affiliation":[{"name":"Myology Institute University of Florida  Gainesville Florida USA"},{"name":"Department of Pharmacology and Therapeutics, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Abe\u2010Teh","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology, College of Health and Human Performance University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4515-4240","authenticated-orcid":false,"given":"Rachel Y.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Computer and Information Science and Engineering, College of Engineering University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4781-5886","authenticated-orcid":false,"given":"Lan","family":"Wei\u2010LaPierre","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology, College of Health and Human Performance University of Florida  Gainesville Florida USA"},{"name":"Myology Institute University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7401-4398","authenticated-orcid":false,"given":"Elisabeth R.","family":"Barton","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology, College of Health and Human Performance University of Florida  Gainesville Florida USA"},{"name":"Myology Institute University of Florida  Gainesville Florida 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