Homeobox C10 inhibits the osteogenic differentiation potential of mesenchymal stem cells

Abstract

<p><b><i>Purpose:</i></b> Mesenchymal stem cells (MSCs) are a reliable cell source for tissue regeneration. However, the molecular mechanisms underlying the directed differentiation of MSCs remain unclear which impedes potential clinical applications. Recent studies have discovered that Homeobox (HOX) genes are involved in the differentiation regulation of MSCs and bone formation. In this study, we investigate the <i>HOXC10</i> function in the osteogenic differentiation potential of MSCs. <b><i>Materials and Methods:</i></b> Stem cells from apical papilla (SCAPs) and adipose-derived stem cells (ADSCs) were used in this study. Alkaline phosphatase (ALP) activity assays, ALP staining, Alizarin red staining, quantitative calcium analysis, osteogenesis-associated gene expression, and <i>in vivo</i> transplantation experiments were used to study osteogenic differentiation potential. <b><i>Results:</i></b> Our results showed that overexpression of <i>HOXC10</i> in SCAPs inhibited ALP activity and mineralization <i>in vitro</i> and decreased the mRNA expression of collagen alpha-1 (I) chain, bone sialoprotein, osteocalcin, and a key transcription factor, runt-related transcription factor 2, in SCAPs. Depletion of <i>HOXC10</i> promoted osteogenic differentiation in SCAPs <i>in vitro</i>. In addition, <i>in vivo</i> transplantation experiments in nude mice confirmed that SCAPs osteogenesis was triggered when <i>HOXC10</i> was downregulated. Furthermore, depletion of <i>HOXC10</i> also enhanced osteogenic differentiation in ADSCs. <b><i>Conclusions:</i></b> Taken together, these results indicated that <i>HOXC10</i> decreased the MSC osteogenic differentiation potential. Thus, inhibition of <i>HOXC10</i> in MSCs might have the potential to improve tissue regeneration and provide insight into the mechanism underlying the directed differentiation of MSCs.</p