Erythropoietin induces the osteogenesis of periodontal mesenchymal stem cells from healthy and periodontitis sources via activation of the p38 MAPK pathway

Erythropoietin (Epo), a hematopoietic hormone, has multiple biological functions. Recently, the positively osteogenic effects of Epo on mesenchymal stem cells (MSCs) have attracted broad interest. However, the effects of Epo on the osteogenesis of human periodontal ligament tissue-derived mesenchymal stem cells (hPDLSCs) and periodontitis mesenchymal stem cells (pPDLSCs) from patients with periodontitis remain unknown. In the present study, osteogenic effects of Epo on hPDLSCs and pPDLSCs were investigated, and the results suggested that the effects were mediated by promoting the expression of runt related transcription factor 2, alkaline phosphatase (ALP) and osteocalcin. Using Alizarin Red and ALP staining, it was demonstrated that Epo exerted positive osteogenic effects on hPDLSCs and pPDLSCs. Additionally, Epo upregulated the proliferation of hPDLSCs and pPDLSCs, based on flow cytometric analyses of the cell cycle. To determine the underlying mechanism, the role of the p38 mitogen-activated protein kinase (MAPK) pathway, which is associated with the osteogenesis of hPDLSCs and pPDLSCs, was investigated further. Epo increases p38 phosphorylation (the target of the MAPK pathway) in hPDLSCs and pPDLSCs. Furthermore, when the cells were treated with SB203580, an inhibitor of the p38 MAPK pathway, the osteogenic effects of Epo on hPDLSCs and pPDLSCs were attenuated. In conclusion, Epo may upregulate the bone formation ability of hPDLSCs and pPDLSCs via the p38 MAPK pathways.