STRO‐1 confers myofibroblast transdifferentiation in fibroblasts derived from oral submucous fibrosis

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Oral submucous fibrosis (OSF) is an oral potentially malignant disorder of the oral mucosa that predisposes normal mucosa to malignant transformation. In Taiwan, the malignant transformation rate of OSF was reported up to 9.13% during 13‐year follow‐up period.1 OSF is predominantly seen in South‐East Asia and India. The prevalence of OSF in Taiwan increased significantly from 8.3 (per 105) in 1996 to 16.2 (per 105) in 2013.2 Mounting evidence suggests that the habit of areca quid chewing plays an important role in the disease manifestation.3
Traditionally, the pathogenic mechanism of areca quid chewing‐associated OSF was due to excess extracellular matrix proteins accumulation.4 The amounts of myofibroblasts, contractile cells expressing α‐smooth muscle actin (α‐SMA), were found to be correlated with disease severity of OSF for response to the microtrauma by the continuous mechanical irritation from areca quid chewing.5 Therefore, we have established the collagen contraction assay for myofibroblast activities that found the crucial roles of myofibroblast transdifferentiation during the pathogenesis of areca quid chewing‐associated OSF.6
Mesenchymal stem cells (MSCs) possess unique biological characteristics such as plasticity, long‐term self‐renewal, secretion of various bioactive molecules, and ability of active migration to the diseased tissues that provides an ideal fibrosis model to study the role of stemness properties in promoting and maintaining the OSF. The fibrotic nature of OSF suggests that MSCs may serve as primary source of multipotent cells to repopulate the wound site in response to exogenous insults, such as trauma and irritation from areca quid chewing.
STRO‐1, the most well‐known MSC marker, was the first antibody used to prospectively immune‐select a population of cells from human bone marrow that included the entire clonogenic colony‐forming fibroblastic population.10 In oral cavity, STRO‐1 has been utilized for the selection of PDL stem cells,11 dental pulp stem cells,12 and apical papilla‐derived stem cells.13 Moreover, STRO‐1 was found to display in hyperplastic gingival propria14 and chronic hyperplastic pulp polyp.15 This indicates that STRO‐1 may play an important role in the pathogenesis of fibrotic changes. Therefore, the role of STRO‐1 in OSF remains to be further investigated.
The present work was undertaken to identify the in situ localization of STRO‐1 expression in normal buccal mucosa and OSF specimens. More specifically, we have therefore measured the relative levels of STRO‐1 in fibroblasts derived from normal buccal mucosa (BMFs) compared with OSF (OSFFs) and a major areca nut alkaloid arecoline was added to explore the expression of STRO‐1 in normal human BMFs in vitro. Compared the activities between sorted STRO‐1+ and STRO‐1− OSFFs were measured by collagen gel contraction, migration, invasion abilities, and the expression of α‐smooth muscle actin (α‐SMA) and pro‐α1 (I) chain of type I collagen.

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