{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:59:35Z","timestamp":1791946775794,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Perturbation in cell adhesion and growth factor signalling in satellite cells results in decreased muscle regenerative capacity. Cdon (also called Cdo) is a component of cell adhesion complexes implicated in myogenic differentiation, but its role in muscle regeneration remains to be determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated inducible satellite cell\u2010specific Cdon ablation in mice by utilizing a conditional\n                      <jats:italic>Cdon<\/jats:italic>\n                      allele and\n                      <jats:italic>\n                        Pax7\n                        <jats:sup>CreERT2<\/jats:sup>\n                      <\/jats:italic>\n                      . To induce Cdon ablation, mice were intraperitoneally injected with tamoxifen (tmx). Using cardiotoxin\u2010induced muscle injury, the effect of Cdon depletion on satellite cell function was examined by histochemistry, immunostaining, and 5\u2010ethynyl\u20102'\u2010deoxyuridine (EdU) incorporation assay. Isolated myofibers or myoblasts were utilized to determine stem cell function and senescence. To determine pathways related to Cdon deletion, injured muscles were subjected to RNA sequencing analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Satellite cell\u2010specific\n                      <jats:italic>Cdon<\/jats:italic>\n                      ablation causes impaired muscle regeneration with fibrosis, likely attributable to decreased proliferation, and senescence, of satellite cells. Cultured Cdon\u2010depleted myofibers exhibited 32 \u00b1 9.6% of EdU\u2010positive satellite cells compared with 58 \u00b1 4.4% satellite cells in control myofibers (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). About 32.5 \u00b1 3.7% Cdon\u2010ablated myoblasts were positive for senescence\u2010associated \u03b2\u2010galactosidase (SA\u2010\u03b2\u2010gal) while only 3.6 \u00b1 0.5% of control satellite cells were positive (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001). Transcriptome analysis of muscles at post\u2010injury Day 4 revealed alterations in genes related to mitogen\u2010activated protein kinase signalling (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 8.29 e\n                      <jats:sup>\u22125<\/jats:sup>\n                      ) and extracellular matrix (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 2.65 e\n                      <jats:sup>\u221224<\/jats:sup>\n                      ). Consistent with this, Cdon\u2010depleted tibialis anterior muscles had reduced phosphorylated extracellular signal\u2010regulated kinase (p\u2010ERK) protein levels and expression of ERK targets, such as\n                      <jats:italic>Fos<\/jats:italic>\n                      (0.23\u2010fold) and\n                      <jats:italic>Egr1<\/jats:italic>\n                      (0.31\u2010fold), relative to mock\u2010treated control muscles (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001). Cdon\u2010depleted myoblasts exhibited impaired ERK activation in response to basic fibroblast growth factor. Cdon ablation resulted in decreased and\/or mislocalized integrin \u03b21 activation in satellite cells (weak or mislocalized integrin1 in tmx = 38.7 \u00b1 1.9%, mock = 21.5 \u00b1 6%,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05), previously linked with reduced fibroblast growth factor (FGF) responsiveness in aged satellite cells. In mechanistic studies, Cdon interacted with and regulated cell surface localization of FGFR1 and FGFR4, likely contributing to FGF responsiveness of satellite cells. Satellite cells from a progeria model,\n                      <jats:italic>Zmpste24<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      myofibers, showed decreased Cdon levels (Cdon\u2010positive cells in Zmpste24\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      = 63.3 \u00b1 11%, wild type = 90 \u00b1 7.7%,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05) and integrin \u03b21 activation (weak or mislocalized integrin \u03b21 in Zmpste24\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      = 64 \u00b1 6.9%, wild type = 17.4 \u00b1 5.9%,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cdon deficiency in satellite cells causes impaired proliferation of satellite cells and muscle regeneration via aberrant integrin and FGFR signalling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12563","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T03:32:40Z","timestamp":1582774360000},"page":"1089-1103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Satellite cell\u2010specific ablation of\n                    <i>Cdon<\/i>\n                    impairs integrin activation, FGF signalling, and muscle regeneration"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1638-6820","authenticated-orcid":false,"given":"Ju\u2010Hyeon","family":"Bae","sequence":"first","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon Republic of Korea"},{"name":"Single Cell Network Research Center Sungkyunkwan University 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