{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:15:37Z","timestamp":1788344137203,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271017"],"award-info":[{"award-number":["82271017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2023NSFSC0034"],"award-info":[{"award-number":["2023NSFSC0034"]}],"id":[{"id":"10.13039\/501100018542","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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Orofacial and limb muscles differ in embryonic origin and regenerative capacity. Neuromuscular junction (NMJ) regeneration is critical for muscle restoration both histologically and functionally. The relative potential of orofacial and limb muscles to form postsynaptic apparatuses remains elusive. While the role of fibro\u2010adipogenic progenitors (FAPs) in NMJ regeneration has been discussed in limb muscles, it remains unexplored in orofacial muscles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NMJ regeneration was triggered by freeze injury in masseter (MAS) and tibialis anterior (TA) muscles and assessed using histological and functional tests. FAPs transplantation experiments and coculture with muscle stem cells (MuSCs) were performed to investigate their effects on postsynaptic apparatus formation. Transcriptome profiling of FAPs identified the key secretory molecule involved in NMJ regulation. The effect of this molecule was further investigated using in\u00a0vitro gain\u2010 and loss\u2010of\u2010function assays, conditional knockout transgenic mice and pharmacological blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Immunohistochemistry showed extensive fibrosis surrounded by regenerated myofibres in MAS, whereas no fibrosis but regenerated myofibres in TA. Restored myofibre calibre and resolved fibrosis in the regenerated lesion periphery are observed in both muscles, yet regenerated NMJs remained markedly below the intact level at 30\u2009days post\u2010injury (dpi) only in MAS (\u221252.1%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Interestingly, transplantation of FAPs isolated from MAS reduced the number of postsynaptic acetylcholine receptors (AChRs) on regenerated myofibres in recipient TA muscle (\u221261.3%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Conditioned medium of FAPs isolated from MAS at 7\u2009dpi impaired AChR clustering on myotubes, decreasing the AChR\/myotube area ratio (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). RNA\u2010seq analysis of 7\u2009dpi MAS and TA FAPs identified myostatin (\n                      <jats:italic>Mstn<\/jats:italic>\n                      ) as the key differentially expressed gene.\n                      <jats:italic>Mstn<\/jats:italic>\n                      transcripts in MAS FAPs were 1.7\u2010fold higher than those in TA FAPs (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In\u00a0vitro knockdown of\n                      <jats:italic>Mstn<\/jats:italic>\n                      in FAPs isolated from 7\u2009dpi MAS reversed its negative effect on AChR clustering, as evidenced by a 4\u2010fold increase in the AChR\/myotube area ratio (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). The number of nascent AChR clusters in injured MAS of FAP\u2010specific\n                      <jats:italic>Mstn<\/jats:italic>\n                      knockout mice was higher than that of injured floxed controls (2.7\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Pharmacological blockade of MSTN enhanced postsynaptic AChR neogenesis in MAS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrated differential NMJ regeneration in MAS and TA muscle. Injury\u2010activated MAS FAPs impede postsynaptic apparatus formation by secreting pathophysiological levels of MSTN. Lowering MSTN levels in injured MAS might enhance its regeneration through nerve\u2010muscle signalling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70264","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T04:16:23Z","timestamp":1775103383000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fibro\u2010Adipogenic Progenitors Regulate Orofacial Neuromuscular Junction Regeneration via Myostatin"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9373-1246","authenticated-orcid":false,"given":"Ruizhi","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomotology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Orthodontics, West China Hospital of Stomatology Sichuan University  Chengdu 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