Syringetin, a flavonoid derivative in grape and wine, induces human osteoblast differentiation through bone morphogenetic protein-2/extracellular signal-regulated kinase 1/2 pathway
Syringetin, a flavonoid derivative in grape and wine, induces human osteoblast differentiation through bone morphogenetic protein-2/extracellular signal-regulated kinase 1/2 pathway
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DOI：
10.1002/mnfr.200800483
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发表时间：
2009-11-01
影响因子：
5.2
通讯作者：
Kuo, Po-Lin
中科院分区：
文献类型：
--
作者：
Hsu, Ya-Ling;Liang, Hsin-Lin;Kuo, Po-Lin
丁香素(3，5，7，4‘-tetrahydroxy-3’，5‘dimethoxyflavone)，是一种类黄酮衍生物，存在于葡萄和葡萄酒中。通过碱性磷酸酶(ALP)活性、骨钙素和I型胶原酶联免疫吸附试验，我们发现丁香素对MC3T3-E1小鼠颅骨成骨细胞和人胎骨成骨1.19细胞系人成骨细胞具有明显的诱导分化作用。碱性磷酸酶和骨钙素分别是早期分化成骨细胞和晚期分化成骨细胞的表型标志物。我们的结果表明，丁香素刺激成骨细胞分化的不同阶段，从成熟到终末分化的成骨细胞。丁香素诱导分化与骨形态发生蛋白-2(BMP-2)的产生增加有关。BMP-2拮抗剂noggin阻断了丁香素介导的碱性磷酸酶活性和骨钙素分泌的增强，表明BMP-2的产生是丁香素介导的成骨细胞成熟和分化所必需的。紫丁香素诱导分化与Smad1/5/8和细胞外信号调节蛋白1/2(ERK1/2)的激活有关。ERK1/2抑制剂2‘-氨基-3’-甲氧基黄酮合用可抑制丁香素介导的碱性磷酸酶上调和骨钙素的产生。综上所述，丁香素促进BMP-2的合成，进而激活Smad1/5/8和ERK1/2，这一作用可能与其诱导成骨细胞成熟分化，进而增加骨量有关。
Syringetin (3,5,7,4'-tetrahydroxy-3',5'dimethoxyflavone), a flavonoid derivative, is present in grape and wine. By means of alkaline phosphatase (ALP) activity, osteocalcin, and type I collagen ELISA, we have shown that syringetin exhibits a significant induction of differentiation in MC3T3-E1 mouse calvaria osteoblasts and human fetal osteoblastic 1.19 cell line human osteoblasts. ALP and osteocalcin are phenotypic markers for early-stage differentiated osteoblasts and terminally differentiated osteoblasts, respectively. Our results indicate that syringetin stimulates osteoblast differentiation at various stages, from maturation to terminally differentiated osteoblasts. Induction of differentiation by syringetin is associated with increased bone morphogenetic protein-2 (BMP-2) production. The BMP-2 antagonist noggin blocked syringetin-mediated ALP activity and osteocalcin secretion enhancement, indicating that BMP-2 production is required in syringetin-mediated osteoblast maturation and differentiation. induction of differentiation by syringetin is associated with increased activation of SMAD1/5/8 and extracellular signal-regulated kinase 1/2 (ERK1/2). Cotreatment of ERK1/2 inhibitor 2'-amino-3'-methoxyflavone inhibited syringetin-mediated ALP upregulation and osteocalcin production. In conclusion, syringetin increased BMP-2 synthesis, and subsequently activated SMAD1/5/8 and ERK1/2, and this effect may contribute to its action on the induction of osteoblast maturation and differentiation, followed by an increase of bone mass.