Strontium fructose 1,6-diphosphate prevents bone loss in a rat model of postmenopausal osteoporosis via the OPG/RANKL/RANK pathway
Strontium fructose 1,6-diphosphate prevents bone loss in a rat model of postmenopausal osteoporosis via the OPG/RANKL/RANK pathway
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DOI：
10.1038/aps.2011.177
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发表时间：
2012-04-01
影响因子：
8.2
通讯作者：
Ying, Han-jie
中科院分区：
文献类型：
--
作者：
Ma, Bo;Zhang, Qi;Ying, Han-jie
目的：评价1，6-二磷酸果糖锶盐(FDP-SR)对去卵巢大鼠骨质疏松模型的骨保护作用。方法：将80只雌性SD大鼠随机分为去卵巢(OVX)组和假手术组。3个月后，将大鼠分为6组，每组10只：假手术组、去卵巢对照组、去卵巢+FDP-锶(110、220、440 mg/kg)组、去卵巢+雷尼酸锶(SR，180 mg/kg)组。口服给药3个月。治疗结束后，测定骨密度(BMD)、股骨和腰椎生物力学性能、骨小梁组织形态、血清磷、钙、骨特异性碱性磷酸酶(B-ALP)、抗酒石酸酸性磷酸酶5b(TRACP5b)、I型胶原N-端肽(NTX)和一系列氧化应激指标。用双抗体夹心法测定血清中核因子-KB受体激活剂配体(RANKL)和护骨素(OPG)水平，用RT-PCR法检测其在骨组织中的基因表达水平。结果：FDP-SR(220、440 mg/kg)或SR(180 mg/kg)可显著增加去势大鼠的骨密度，改善骨微结构和骨强度。降低去卵巢大鼠血清和骨髓中H202和MDA水平，恢复血清和骨髓中CAT水平，升高血清B-ALP水平，降低NTX和TRACP5b水平。FDP-sr可降低血清RANKL水平，升高血清OPG水平，并呈剂量依赖关系。显著下调骨髓RANKL的表达，上调OPG的表达。结论：FDP-sR可能是治疗绝经后骨质疏松症的有效药物，其部分作用机制是通过OPG-RANKL-RANK途径降低IQ破骨细胞生成。
Aim: To evaluate the protective effects of strontium fructose 1,6-diphosphate (FDP-Sr), a novel strontium salt that combined fructose 1,6-diphosphate (FDP) with strontium, on bone in an ovariectomy-induced model of bone loss. Methods: Eighty female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Three months later, the rats were assigned to six groups (10 for each): sham-operated, OVX control, OVX+FDP-Sr (110, 220, or 440 mg/kg), or OVX+strontium ranelate (SR, 180 mg/kg). Drugs were administered orally for 3 months. When the treatment was terminated, the following parameters were assessed: bone mineral density (BMD), the biomechanical properties of the femur and lumbar vertebrae, trabecular histomorphology, serum phosphorus, calcium, bone-specific alkaline phosphatase (B-ALP), tartrate-resistant acid phosphatase 5b (TRACP5b), N-telopeptide of type I collagen (NTx) and a series of markers for oxidative stress. Receptor activator of NF-KB ligand (RANKL) and osteoprotegerin (OPG) levels in serum were measured using ELISA and their gene expression levels in the bone were measured using R-T PCR. Results: Treatment with FDP-Sr (220 or 440 mg/kg) or SR (180 mg/kg) significantly increased the BMD and improved the bone microarchitecture and bone strength in OVX rats. The treatments also decreased in the levels of H202 and MDA, restored the CAT level in serum and bone marrow, increased the serum B-ALP and decreased NTx and TRACP 5b in OVX rats. Treatment with FDP-Sr decreased the RANKL level, and increased the OPG level in serum in a dose-dependent manner. It also significantly down-regulated the RANKL expression and up-regulated OPG expression in bone marrow. Conclusion: FDP-Sr may be an effectve treatenent for postmenopausal osteoporosis that acts, in part, via a decrease iq osteoclastogenesis through the OPG \RANKL\RANK pathway.