Oriental Medicine Research Center for Bone & Joint Disease, KyungHee University, 149, Sangil-dong, Gangdong-gu, Seoul, 134-727, Republic of Korea.
Int Immunopharmacol. 2009 Nov;9(12):1357-65. doi: 10.1016/j.intimp.2009.08.003. Epub 2009 Aug 17.
Plant-derived phytoestrogens have bone protective effects, but the molecular mechanism behind these effects remains unclear. This study is aimed at fully characterizing the fracture healing process of formononetin, and investigating the mechanism underlying angiogenesis in calluses of a rat fracture model. Femoral fractures were produced in 2-month-old Sprague-Dawley rats. A 20 microg/kg or 200 microg/kg dose of formononetin was orally administrated once a day during the healing period of 21 days. The results showed that in the early stage of chondrogenesis (days 3), formononetin significantly increased the number of vessels, and expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2/flk-1) compared with control. However, the larger dose of formononetin had no significant difference on expression of VEGF and VEGFR-2/Flk-1 compared with that of the smaller dose of formononetin. After 7 days of administration, formononetin markedly induced differentiation of mesenchymal stem cells in the fracture site. After 14 days, gene expression of mesenchymal progenitors such as alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN) and collagen type I (Col I), indicating osteogenic differentiation, was markedly stimulated by formononetin compared with control. These results suggest that formononetin promotes early fracture healing through angiogenesis activation in the early stage of fracture repair, and osteogenesis acceleration in the later stages, and thus may be beneficial for fracture healing.
植物雌激素具有保护骨骼的作用，但这些作用的分子机制尚不清楚。本研究旨在全面描述芒柄花素在骨折愈合过程中的作用，并研究大鼠骨折模型骨痂血管生成的机制。在 2 月龄 Sprague-Dawley 大鼠中造成股骨骨折。在 21 天的愈合期内，每天口服 20μg/kg 或 200μg/kg 的芒柄花素。结果表明，在软骨形成的早期（第 3 天），与对照组相比，芒柄花素显著增加了血管数量，以及血管内皮生长因子（VEGF）和血管内皮生长因子受体 2（VEGFR-2/flk-1）的表达。然而，较大剂量的芒柄花素在 VEGF 和 VEGFR-2/Flk-1 的表达上与较小剂量的芒柄花素相比没有显著差异。给药 7 天后，芒柄花素明显诱导骨折部位间充质干细胞的分化。14 天后，碱性磷酸酶（ALP）、骨钙素（OCN）、骨桥蛋白（OPN）和 I 型胶原（Col I）等间充质前体细胞的基因表达明显受到芒柄花素的刺激，表明成骨分化。这些结果表明，芒柄花素通过在骨折修复的早期阶段激活血管生成，以及在后期阶段加速成骨，从而促进早期骨折愈合，可能有利于骨折愈合。
