<scp>STRO</scp>‐1 confers myofibroblast transdifferentiation in fibroblasts derived from oral submucous fibrosis

<jats:sec><jats:title>Background</jats:title><jats:p><jats:styled-content style="fixed-case">STRO</jats:styled-content>‐1 is a mesenchymal cell marker present on all clonogenic stromal precursors. Current evidence has indicated that the pathogenesis of fibrotic changes may be mediated by stemness properties. The aim of this study was to investigate the role of <jats:styled-content style="fixed-case">STRO</jats:styled-content>‐1 in areca quid chewing‐associated oral submucous fibrosis (<jats:styled-content style="fixed-case">OSF</jats:styled-content>).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Thirty <jats:styled-content style="fixed-case">OSF</jats:styled-content> specimens and ten normal buccal mucosae were examined by immunohistochemistry. The activity of STRO‐1 from fibroblasts cultured from normal buccal mucosa (BMFs) and OSF (OSFFs) were measureed and the effect of arecoline, a major areca nut alkaloid, on STRO‐1 in BMFs was evaluated. Compared the activities between sorted <jats:styled-content style="fixed-case">STRO</jats:styled-content>‐1<jats:sup>+</jats:sup> cells and <jats:styled-content style="fixed-case">STRO</jats:styled-content>‐1<jats:sup>−</jats:sup> cells from <jats:styled-content style="fixed-case">OSFF</jats:styled-content> were measured by collagen gel contraction, migration, invasion abilities, and the expression of α‐smooth muscle actin (α‐<jats:styled-content style="fixed-case">SMA</jats:styled-content>) and pro‐α1 (I) chain of type I collagen.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Our results first showed that the expression of <jats:styled-content style="fixed-case">STRO</jats:styled-content>‐1 was more evident in areca quid chewing‐associated <jats:styled-content style="fixed-case">OSF</jats:styled-content> than normal buccal mucosa tissues (<jats:italic>P</jats:italic> < .05). Arecoline dose‐dependently activated the level of <jats:styled-content style="fixed-case">STRO</jats:styled-content>‐1 in <jats:styled-content style="fixed-case">BMF</jats:styled-content>s (<jats:italic>P</jats:italic> < .05). The relative expression of <jats:styled-content style="fixed-case">STRO</jats:styled-content>‐1 was significantly higher in <jats:styled-content style="fixed-case">OSFF</jats:styled-content>s compared with <jats:styled-content style="fixed-case">BMF</jats:styled-content>s (<jats:italic>P</jats:italic> < .05). In addition, the sorted <jats:styled-content style="fixed-case">STRO</jats:styled-content>‐1<jats:sup>+</jats:sup> cells from <jats:styled-content style="fixed-case">OSFF</jats:styled-content>s exhibited higher collagen gel contraction, migration, and invasion abilities as well as elevated expression of α‐<jats:styled-content style="fixed-case">SMA</jats:styled-content> and pro‐α1 (I) chain of type I collagen than the negative subset (<jats:italic>P</jats:italic> < .05).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These findings suggested that the stemness marker <jats:styled-content style="fixed-case">STRO</jats:styled-content>‐1 may be a crucial factor in the pathogenesis of areca quid chewing‐associated <jats:styled-content style="fixed-case">OSF</jats:styled-content>.</jats:p></jats:sec>