Benvenuti S, Tanini A, Frediani U, Bianchi S, Masi L, Casano R, Bufalino L, Serio M, Brandi M L
Department of Clinical Physiopathology, Florence University School of Medicine, Italy.
J Bone Miner Res. 1991 Sep;6(9):987-96. doi: 10.1002/jbmr.5650060913.
Protective effects of ipriflavone, an isoflavone derivative, in osteoporosis are believed to be caused by the inhibitory action on bone resorption. A direct effect of ipriflavone on bone formation is as yet unknown. Ipriflavone and four of its metabolites (I, II, III, and V) were examined for their effects on parathyroid hormone response, collagen synthesis, alkaline phosphatase activity, and cell proliferation in a clonal cell population of rat osteoblastic cells. Pretreatment of osteoblasts with high concentrations of ipriflavone for 48 h significantly inhibited the cAMP response to parathyroid hormone, producing a shift in the dose-response curve; at lower concentrations metabolites II and III potentiated the cAMP accumulation induced by low doses of parathyroid hormone. The 48 h treatment with metabolite V at the 1 nM dose significantly stimulated collagen synthesis in osteoblastic cells. Ipriflavone and metabolite I showed a biphasic stimulatory action on the alkaline phosphatase activity of osteoblasts, with a maximal effect at the 0.1 and 1 nM doses, respectively. A similar biphasic response was observed with ipriflavone and metabolite I on osteoblastic cell growth, with a maximal effect at the 0.1 nM concentration. These results suggest a direct role of ipriflavone in modulating the synthetic and growth properties of osteoblast-like cells.
异黄酮衍生物依普黄酮在骨质疏松症中的保护作用被认为是由其对骨吸收的抑制作用引起的。依普黄酮对骨形成的直接作用尚不清楚。研究了依普黄酮及其四种代谢产物（I、II、III和V）对大鼠成骨细胞克隆细胞群体中甲状旁腺激素反应、胶原蛋白合成、碱性磷酸酶活性和细胞增殖的影响。用高浓度依普黄酮预处理成骨细胞48小时可显著抑制对甲状旁腺激素的cAMP反应，使剂量反应曲线发生偏移；在较低浓度下，代谢产物II和III可增强低剂量甲状旁腺激素诱导的cAMP积累。1 nM剂量的代谢产物V处理48小时可显著刺激成骨细胞中的胶原蛋白合成。依普黄酮和代谢产物I对成骨细胞的碱性磷酸酶活性表现出双相刺激作用，分别在0.1和1 nM剂量时达到最大效应。依普黄酮和代谢产物I对成骨细胞生长也观察到类似的双相反应，在0.1 nM浓度时达到最大效应。这些结果表明依普黄酮在调节成骨样细胞的合成和生长特性方面具有直接作用。
