Evidence for a role of p38 MAP kinase in expression of alkaline phosphatase during osteoblastic cell differentiation
Evidence for a role of p38 MAP kinase in expression of alkaline phosphatase during osteoblastic cell differentiation
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DOI：
10.1016/s8756-3282(01)00660-3
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发表时间：
2002-01-01
期刊：
影响因子：
4.1
通讯作者：
Caverzasio, J
中科院分区：
文献类型：
--
作者：
Suzuki, A;Guicheux, J;Caverzasio, J
在本研究中，我们研究了丝裂原激活蛋白激酶 (MAPK) Erk、p38 和 JNK 在介导胎牛血清 (FCS) 对 MC3T3-E1 成骨细胞样细胞分化的影响中的意义。 Erk 在增殖、早期分化以及成熟细胞中受到 FCS 的刺激。在增殖细胞中未检测到 FCS 对 p38 的激活，但在细胞分化时观察到。 JNK 在整个分化过程中响应 FCS 而被激活，但在早期分化细胞中观察到最大的刺激。分别使用特定抑制剂（例如 U0126 和 SB203580）确定 Erk 和 p38 通路在介导 MC3T3-E1 细胞分化中的作用。这些实验证实Erk途径对于介导响应FCS的细胞增殖至关重要，但表明该MAP激酶在调节MC3T3-E1细胞的分化方面作用不大。相比之下，p38 仅对增殖产生轻微影响，但似乎对于控制分化细胞中碱性磷酸酶 (ALP) 的表达至关重要。最后，用高剂量的 SB203580 获得的结果也影响 JNK 活性，表明 p38 和/或 JNK 可能还参与分化细胞中 I 型胶原和骨钙蛋白表达的控制。数据表明 MAPK 响应 FCS 调节 MC3T3-E1 细胞发育的不同阶段。不同的 MAPK 通路似乎独立调节成骨细胞增殖和分化，其中 Erk 在细胞复制中发挥重要作用，而 p38 参与成骨细胞分化过程中 ALP 表达的调节。 JNK也可能参与成骨细胞分化的调节，但其确切作用需要进一步研究。 (C) 2002 年，Elsevier Science Inc. 保留所有权利。
In the present study, we investigate the implication of the mitogen-activated protein kinases (MAPKs) Erk, p38, and JNK in mediating the effect of fetal calf serum (FCS) on the differentiation of MC3T3-E1 osteoblast-like cells. Erk is stimulated by FCS in proliferating, early-differentiating, as well as in mature cells. Activation of p38 by FCS is not detected in proliferating cells but is observed as the cells differentiate. JNK is activated in response to FCS throughout the entire differentiation process, but a maximal stimulation is observed in early differentiating cells. The roles of Erk and p38 pathways in mediating MC3T3-E1 cell differentiation was determined using specific inhibitors such as U0126 and SB203580, respectively. These experiments confirmed that the Erk pathway is essential for mediating cell proliferation in response to FCS, but indicated that this MAP kinase has little effect in regulating the differentiation of MC3T3-E1 cells. In contrast, p38 only marginally influenced proliferation, but appeared to be critical for the control of alkaline phosphatase (ALP) expression in differentiating cells. Finally, results obtained with high doses of SB203580, which also affected JNK activity, suggest that p38 and/or JNK are probably also involved in the control of type I collagen and osteocalcin expression in differentiating cells. The data indicate that MAPKs regulate different stages of MC3T3-E1 cell development in response to FCS. Distinct MAPK pathways seem to independently modulate osteoblastic cell proliferation and differentiation, with Erk playing an essential role in cell replication, whereas p38 is involved in the regulation of ALP expression during osteoblastic cell differentiation. JNK is also probably involved in the regulation of osteoblastic cell differentiation, but its precise role requires further investigation. (C) 2002 by Elsevier Science Inc. All rights reserved.