期刊
ACTA PHARMACOLOGICA SINICA
卷 33, 期 4, 页码 479-489出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/aps.2011.177
关键词
osteoporosis; ovariectomy; strontium fructose 1,6-diphosphate; strontium ranelate; osteoprotegerin (OPG); receptor activator of NE-KB ligand (RANKL); bone mineral density; tartrate-resistant acid phosphatase 5 (TRACP5); N-telopeptide of type I collagen (NTx)
资金
- National Natural Science Foundation of China [30873112]
- Six Talent Peek Project of Jiangsu Province [07-C-018]
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.
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