Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Acta Pharmacol Sin. 2012 Jan;33(1):66-74. doi: 10.1038/aps.2011.136. Epub 2011 Nov 28.
To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats.
Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor κB ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in in vitro study. The cells were treated with genistein (10(-7) or 10(-4) mol/L) for 48 h. The expression of the bone homeostasis-associated factors and estrogen receptors (ERs) was detected using real-time PCR, and ER silencing was performed.
At both the low- and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone in vivo. In both in vivo and in vitro study, the low-dose genistein significantly increased the expression of ALP, OC and OPG, but decreased the expression of RANKL and the RANKL/OPG ratio. The high-dose genistein decreased the expression of all these bone homeostasis-associated factors. Both the low and high doses of genistein significantly increased the expression of ERβ, while ERα expression was increased by the low dose genistein and decreased by the high dose genistein. ERβ silencing abrogated most of the effects of genistein treatment.
In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ERβ.
研究金雀异黄素对大鼠下颌髁突软骨下骨骨稳态的影响。
通过灌胃给予雌性 SD 大鼠金雀异黄素（10 和 50mg/kg）或安慰剂 6 周。然后处死动物，分别通过 HE 染色和 micro-CT 分析检测下颌髁突的组织形态学和微观结构。使用实时 PCR 检测下颌髁突中碱性磷酸酶（ALP）、骨钙素（OC）、骨保护素（OPG）、核因子 κB 受体激活剂配体（RANKL）和雌激素受体（ERs）的表达水平。从大鼠下颌髁突中制备培养的成骨细胞进行体外研究。用金雀异黄素（10(-7)或 10(-4)mol/L）处理细胞 48 小时。使用实时 PCR 检测骨稳态相关因子和雌激素受体（ERs）的表达，并进行 ER 沉默。
在低剂量和高剂量下，金雀异黄素均显著增加骨密度（BMD）和骨量，并导致体内软骨下骨小梁变厚。在体内和体外研究中，低剂量金雀异黄素均显著增加 ALP、OC 和 OPG 的表达，而降低 RANKL 和 RANKL/OPG 比值的表达。高剂量金雀异黄素降低了所有这些与骨稳态相关的因子的表达。低剂量和高剂量的金雀异黄素均显著增加 ERβ的表达，而低剂量金雀异黄素增加 ERα的表达，高剂量金雀异黄素降低 ERα的表达。ERβ 沉默消除了金雀异黄素处理的大部分作用。
在大鼠下颌髁突软骨下骨中，低剂量金雀异黄素增加骨形成并抑制骨吸收，而过量金雀异黄素抑制骨形成和吸收。金雀异黄素的作用主要通过 ERβ介导。
