BMP2/7 heterodimer enhances osteogenic differentiation of rat BMSCs via ERK signaling compared with respective homodimers
BMP2/7 heterodimer enhances osteogenic differentiation of rat BMSCs via ERK signaling compared with respective homodimers
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DOI：
10.1002/jcb.28162
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发表时间：
2019-05-01
影响因子：
4
通讯作者：
Liu, Fangjun
中科院分区：
文献类型：
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作者：
Miao, Chunlei;Qin, Dengke;Liu, Fangjun
骨形态发生蛋白（BMP）2/7异二聚体在促进骨再生方面显示出更大的功效。然而，在BMP 2/7驱动的成骨中，丝裂原活化蛋白激酶（MAPK）信号网络的确切机制和作用仍不清楚。在这项研究中，我们评估了BMP 2/-7异二聚体对大鼠骨髓间充质干细胞（BMSCs）成骨分化的影响，目的是阐明MAPKs如何参与这一细胞过程，通过用BMP 2/-7与一种特殊的信号通路抑制剂处理大鼠BMSCs。我们发现BMP 2/7异二聚体诱导大鼠BMSCs的成骨反应比同二聚体强得多。最有趣的是，在BMP 2/7异二聚体处理组中，细胞外信号调节激酶（ERK）表现出高度持续的磷酸化和激活，并且使用U 0126特异性抑制剂抑制ERK级联反应，显著降低BMP 2/7异二聚体处理的大鼠BMSCs中ALP和钙矿化的活性。总的来说，我们证明了BMP 2/7异源二聚体在大鼠BMSCs中显示出强有力的刺激成骨的能力。参与这一过程的活化ERK信号通路可能部分有助于异源二聚体BMP 2/7生长因子的成骨潜能增加。
Bone morphogenetic protein (BMP)2/7 heterodimer shows greater efficacy in enhancing bone regeneration. However, the precise mechanism and the role of mitogen-activated protein kinase (MAPK) signaling network in BMP2/7-driven osteogenesis remain ambiguous. In this study, we evaluated the effects of BMP2/7 heterodimers on osteoblastic differentiation in rat bone marrow mesenchymal stem cells (BMSCs), with the aim to elaborate how MAPKs might be involved in this cellular process by treatment of rat BMSCs with BMP2/-7 with a special signal-pathway inhibitor. We found that BMP2/7 heterodimer induced a much stronger osteogenic response in rat BMSCs compared with either homodimer. Most interestingly, extracellular signal-regulated kinase (ERK) demonstrated a highly sustained phosphorylation and activation in the BMP2/7 heterodimer treatment groups, and inhibition of ERK cascades using U0126 special inhibitor that significantly reduced the activity of ALP and calcium mineralization to a substantial degree in rat BMSCs treated with BMP2/7 heterodimers. Collectively, we demonstrate that BMP2/7 heterodimer shows a potent ability to stimulate osteogenesis in rat BMSCs. The activated ERK signaling pathway involved in this process may contribute partially to an increased osteogenic potency of heterodimeric BMP2/7 growth factors.