State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Laparoscopic Surgery Department, The 451st Hospital of People's Liberation Army, Xi'an, Shaanxi 710054, P.R. China.
Int J Mol Med. 2018 Feb;41(2):829-835. doi: 10.3892/ijmm.2017.3294. Epub 2017 Nov 28.
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.
促红细胞生成素（Epo）是一种造血激素，具有多种生物学功能。最近，Epo 对间充质干细胞（MSCs）的正向成骨作用引起了广泛关注。然而，Epo 对牙周韧带组织来源的人骨髓间充质干细胞（hPDLSCs）和牙周炎患者来源的间充质干细胞（pPDLSCs）成骨的影响尚不清楚。在本研究中，研究了 Epo 对 hPDLSCs 和 pPDLSCs 的成骨作用，结果表明，这种作用是通过促进 runt 相关转录因子 2、碱性磷酸酶（ALP）和骨钙素的表达来介导的。通过茜素红和 ALP 染色，证明 Epo 对 hPDLSCs 和 pPDLSCs 具有正向成骨作用。此外，通过细胞周期的流式细胞术分析，证明 Epo 可上调 hPDLSCs 和 pPDLSCs 的增殖。为了确定潜在的机制，进一步研究了与 hPDLSCs 和 pPDLSCs 成骨相关的丝裂原活化蛋白激酶（MAPK）途径中 p38 的作用。Epo 增加了 hPDLSCs 和 pPDLSCs 中 p38 的磷酸化（MAPK 途径的靶点）。此外，当用 p38 MAPK 途径抑制剂 SB203580 处理细胞时，Epo 对 hPDLSCs 和 pPDLSCs 的成骨作用减弱。综上所述，Epo 可能通过 p38 MAPK 途径上调 hPDLSCs 和 pPDLSCs 的骨形成能力。
