Erythropoietin Promotes Bone Formation through EphrinB2/EphB4 Signaling
Erythropoietin Promotes Bone Formation through EphrinB2/EphB4 Signaling
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DOI：
10.1177/0022034514566431
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发表时间：
2015-03-01
影响因子：
7.6
通讯作者：
Sun, H.
中科院分区：
文献类型：
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作者：
Li, C.;Shi, C.;Sun, H.
近年来的研究表明，促红细胞生成素(EPO)具有广泛的非造血生物学功能。然而，尽管一些研究表明EPO可以影响骨稳态，但人们对EPO如何调控骨形成知之甚少。在这项研究中，我们研究了EPO对破骨细胞和成骨细胞之间通过ewitinB2/EphB4信号通路进行通讯的影响。我们发现EPO通过增加ST2细胞中EphB4的表达来轻微促进成骨细胞的分化。而促红细胞生成素可上调RAW264.7细胞中NFATc1和eaffinB2的表达，而下调Mmp9的表达，从而导致破骨细胞中eaffinB2的表达增加，骨吸收活性降低。在ST2细胞中，EphB4信号通路的激活可显著促进EPO介导的成骨细胞分化。通过EphB4 shRNA敲除EphB4可抑制EPO介导的成骨细胞表型。此外，体内试验清楚地表明，EPO在牙槽骨再生模型中有效地诱导新骨形成。综上所述，这些结果提示ePhinB2/EphB4信号可能在EPO介导的骨形成中发挥重要作用。
Recent studies have demonstrated that erythropoietin (EPO) has extensive nonhematopoietic biological functions. However, little is known about how EPO regulates bone formation, although several studies suggested that EPO can affect bone homeostasis. In this study, we investigated the effects of EPO on the communication between osteoclasts and osteoblasts through the ephrinB2/EphB4 signaling pathway. We found that EPO slightly promotes osteoblastic differentiation with the increased expression of EphB4 in ST2 cells. However, EPO increased the expression of Nfatc1 and ephrinB2 but decreased the expression of Mmp9 in RAW264.7 cells, resulting in an increase of ephrinB2-expressing osteoclasts and a decrease in resorption activity. The stimulation of ephrinB2/EphB4 signaling via ephrinB2-Fc significantly promoted EPO-mediated osteoblastic differentiation in ST2 cells. EphB4 knockdown through EphB4 shRNA inhibited EPO-mediated osteoblastic phenotypes. Furthermore, in vivo assays clearly demonstrated that EPO efficiently induces new bone formation in the alveolar bone regeneration model. Taken together, these results suggest that ephrinB2/EphB4 signaling may play an important role in EPO-mediated bone formation.