The Prenyl Group Contributes to Activities of Phytoestrogen 8-Prenynaringenin in Enhancing Bone Formation and Inhibiting Bone Resorption In Vitro
The Prenyl Group Contributes to Activities of Phytoestrogen 8-Prenynaringenin in Enhancing Bone Formation and Inhibiting Bone Resorption In Vitro
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DOI：
10.1210/en.2012-2086
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发表时间：
2013-03-01
期刊：
影响因子：
4.8
通讯作者：
Chen, Ke-Ming
中科院分区：
文献类型：
--
作者：
Ming, Lei-Guo;Lv, Xiang;Chen, Ke-Ming
以前的研究发现，8-戊烯基黄酮类化合物比类黄酮类化合物具有更高的成骨活性，这表明8-戊烯基基团可能在骨保护特性中发挥积极作用。为了验证这一假说，我们比较了8-戊烯基柚皮苷(PNG)和柚皮苷(NG)在体外对成骨细胞和破骨细胞分化和功能的影响。在培养的大鼠颅骨成骨细胞中，PNG比NG具有更强的促进成骨细胞分化和成骨功能的能力，表现在碱性磷酸酶活性、骨钙素、钙沉积、矿化骨结节的数量和面积以及成骨相关基因BMP-2、OSX和RUNX-2的mRNA表达水平。此外，尽管破骨细胞诱导因子受体激活物核因子-B配体(RANKL)的表达不受影响，但破骨细胞生成抑制因子OPG的表达及OPG/RANKL比值的增加，PNG的作用比NG更强。PNG对兔骨髓破骨细胞的形成及其吸收活性的抑制作用也高于NG，表现为破骨细胞数量减少，骨吸收陷窝的数量和面积减少，抗酒石酸酸性磷酸酶和组织蛋白酶K的mRNA表达水平降低。此外，PNG诱导成熟破骨细胞凋亡的程度和时间也比NG更早。这些结果表明，与NG相比，PNG的8-戊烯基起着重要的作用，并且有助于PNG具有更高的骨保护活性。(内分泌学154：1202-1214,2013)
Previous studies have found that 8-prenylflavonoids have a higher osteogenic activity than do flavonoids, which suggested that the 8-prenyl group may play an active role in bone-protective properties. To address this hypothesis, activities of 8-prenylnaringenin (PNG) and naringenin (NG) in osteoblast and osteoclast differentiation and function were compared in vitro. PNG was found to have a stronger ability than NG to improve osteoblast differentiation and osteogenic function in cultured rat calvarial osteoblasts, as demonstrated by levels of alkaline phosphatase activity, osteocalcin, calcium deposition, and the number and area of mineralized bone nodules, as well as mRNA expression of osteogenesis-related genes Bmp-2, OSX, and Runx-2. In addition, although expression of osteoclastogenic inducer receptor activator of nuclear factor kappa-B ligand (RANKL) was not affected, that of osteoclastogenesis inhibitor osteoprotegerin (OPG) and consequently the OPG/RANKL ratio were increased, more potently by PNG than NG. PNG was also found to have a higher potency than NG in inhibiting the osteoclast formation in rabbit bone marrow cells and their resorptive activity, as revealed by lower numbers of osteoclasts formed, lower numbers and areas of bone resorption pits, and lower mRNA expression levels of tartrate-resistant acid phosphatase and cathepsin K. Furthermore, PNG induced apoptosis of mature osteoclasts at a higher degree and at an earlier time than did NG. These results indicate that the 8-prenyl group plays an important role and contributes to the higher bone-protective activity of PNG in comparison with NG. (Endocrinology 154: 1202-1214, 2013)