Department of Pharmacology, School of Medicine, China Medical University and Hospital, Taichung, Taiwan.
Eur J Pharmacol. 2010 Dec 1;648(1-3):59-66. doi: 10.1016/j.ejphar.2010.08.052. Epub 2010 Sep 17.
Isoflavones are compounds structurally similar to the mammalian estrogens and have received considerable attention for their preventive actions on bone loss. Here, we synthesized the novel isoflavone derivatives and examined their activities in bone cells. We found that the novel isoflavone derivatives markedly inhibited the receptor activator of nuclear factor kappa B ligand (RANKL) plus macrophage colony stimulating factor (M-CSF)-induced osteoclastic differentiation from bone marrow stromal cells and RAW264.7 macrophage cells. Treatment of RAW264.7 macrophages with RANKL-induced extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) phosphorylation. However, RANKL-induced p38 and JNK but not ERK phosphorylation was attenuated by isoflavone derivatives. Furthermore, RANKL-mediated increase of p65 phosphorylation at Ser⁵³⁶, NF-κB-specific DNA-protein complex formation and κB-luciferase activity was inhibited by isoflavone derivatives. On the other hand, isoflavone derivatives did not affect the cell proliferation and differentiation of human cultured osteoblasts. Our data suggest that the novel isoflavone derivatives inhibit osteoclastogenesis from bone marrow stromal cells and macrophage cells via attenuation of RANKL-induced p38, JNK and NF-κB activation.
异黄酮是与哺乳动物雌激素结构相似的化合物，因其对骨质流失的预防作用而受到广泛关注。在这里，我们合成了新型异黄酮衍生物，并研究了它们在骨细胞中的活性。我们发现，新型异黄酮衍生物能显著抑制核因子κB 受体激活剂配体（RANKL）加巨噬细胞集落刺激因子（M-CSF）诱导的骨髓基质细胞和 RAW264.7 巨噬细胞的破骨细胞分化。用 RANKL 诱导 RAW264.7 巨噬细胞细胞外信号调节激酶（ERK）、p38 和 c-Jun N 末端激酶（JNK）磷酸化。然而，异黄酮衍生物减弱了 RANKL 诱导的 p38 和 JNK 但不是 ERK 的磷酸化。此外，RANKL 介导的 p65 在 Ser⁵³⁶的磷酸化、NF-κB 特异性 DNA-蛋白复合物形成和κB-荧光素酶活性的增加被异黄酮衍生物抑制。另一方面，异黄酮衍生物不影响人培养成骨细胞的增殖和分化。我们的数据表明，新型异黄酮衍生物通过抑制 RANKL 诱导的 p38、JNK 和 NF-κB 激活来抑制破骨细胞从骨髓基质细胞和巨噬细胞的分化。
