p75NTR optimizes the osteogenic potential of human periodontal ligament stem cells by up-regulating α1 integrin...

Human periodontal ligament stem cells (hPDLSCs) are a promising source in regenerative medicine. Due to the complexity and heterogeneity of hPDLSCs, it is critical to isolate homogeneous hPDLSCs with high regenerative potential. In this study, p75 neurotrophin receptor (p75NTR) was used to isolate p75NTR⁺ and p75NTR^- hPDLSCs by fluorescence-activated cell sorting. Differences in osteogenic differentiation among p75NTR⁺ , p75NTR^- and unsorted hPDLSCs were observed. Differential gene expression profiles between p75NTR⁺ and p75NTR^- hPDLSCs were analysed by RNA sequencing. α1 Integrin (ITGA1) small interfering RNA and ITGA1-overexpressing adenovirus were used to transfect p75NTR⁺ and p75NTR^- hPDLSCs. The results showed that p75NTR⁺ hPDLSCs demonstrated superior osteogenic capacity than p75NTR^- and unsorted hPDLSCs. Differentially expressed genes between p75NTR⁺ and p75NTR^- hPDLSCs were highly involved in the extracellular matrix-receptor interaction signalling pathway, and p75NTR⁺ hPDLSCs expressed higher ITGA1 levels than p75NTR^- hPDLSCs. ITGA1 silencing inhibited the osteogenic differentiation of p75NTR⁺ hPDLSCs, while ITGA1 overexpression enhanced the osteogenic differentiation of p75NTR^- hPDLSCs. These findings indicate that p75NTR optimizes the osteogenic potential of hPDLSCs by up-regulating ITGA1 expression, suggesting that p75NTR can be used as a novel cell surface marker to identify and purify hPDLSCs to promote their applications in regenerative medicine.