HOXC10 negatively regulates marker-defined neurogenic differentiation of dental pulp stem cells via the BMP7-Smad1/5/9 signaling pathway

Background Dental pulp stem cells (DPSCs) are promising candidates for neural repair, but the transcriptional regulators that restrain or permit their neurogenic response remain incompletely defined. Based on prior evidence that HOXC10 regulates mesenchymal stem-cell fate, we hypothesized that HOXC10 modulates neurogenic induction in DPSCs and that BMP-family signaling may participate in this process. Methods Human DPSCs were isolated and subjected to lentiviral-mediated HOXC10 silencing or overexpression. The endpoint of neurogenic differentiation was defined by changes in neural-lineage marker expression and neuron-like cell morphology, as assessed by immunofluorescence staining, qRT-PCR, and Western blotting; mature neuronal function, including electrophysiological activity, was not evaluated. An ectopic nude-mouse transplantation model was used to evaluate histological marker expression in vivo. Results Partial suppression of HOXC10 increased neurogenic marker expression and promoted neuron-like morphological changes in DPSCs, including increased NESTIN, β-TUBULIN Ⅲ, MAP2, NCAM1 , NES , NeuroD , S100B , and TH . In contrast, enforced HOXC10 expression reduced these marker-based readouts. Similar marker-expression trends were observed in the in vivo transplantation model. Transcriptomic analysis indicated enrichment of TGF-beta/BMP-related signaling among differentially expressed genes after HOXC10 knockdown. Subsequent experiments showed reduced BMP7 expression and Smad1/5/9 phosphorylation in HOXC10-knockdown cells, supporting an association between HOXC10 and the BMP7/Smad1/5/9 axis. Conclusions HOXC10 appears to act as a negative regulator of marker-defined neurogenic differentiation in DPSCs. The data support an association between HOXC10 expression and BMP7/Smad1/5/9 signalling during DPSCs neurogenic induction; however, they do not establish direct transcriptional regulation or pathway causality. These findings provide a basis for further rescue and functional studies of HOXC10 in neural regenerative applications.