Liu Meijie , Wang Ruihai , Li Yan , Bai Dong , Pan Jinghua , Liu Hong , Wang Shaojun , Wu Jiaying , Sun Gang , Miao Qing , Ju Dahong , Liu Limei
{"title":"去卵巢大鼠骨代谢的影响","authors":"Liu Meijie , Wang Ruihai , Li Yan , Bai Dong , Pan Jinghua , Liu Hong , Wang Shaojun , Wu Jiaying , Sun Gang , Miao Qing , Ju Dahong , Liu Limei","doi":"10.1016/S0254-6272(18)30989-0","DOIUrl":null,"url":null,"abstract":"<div><h3>OBJECTIVE</h3><p>To determine the effect of an esculetin formulation (at 97.4% purity) on osteoporosis, and to investigate the potential underlying molecular mechanism(s).</p></div><div><h3>METHODS</h3><p>Sixty specific pathogen free-grade female Wistar rats were randomly assigned to three groups: blank control (<em>n =</em> 12), sham (<em>n =</em> 12), and model (<em>n =</em> 36). The model group were bilaterally ovariectomized. The sham group had the tissue surrounding the ovaries removed, while the ovaries were retained. After 3 months, the model group was randomly divided into three subgroups: OVX (<em>n =</em> 12), positive control (<em>n =</em> 12), and esculetin (<em>n =</em> 12). The positive control group and the esculetin group were intragastrically administered diethylstilbestrol (0.046 mg • kg<sup>−1</sup> • d<sup>−1</sup>) or esculetin (384 mg • kg<sup>−1</sup> • d<sup>−1</sup>), respectively, once per day for 6 consecutive days; medication administration was then stopped for 1 d, before being administered for another 6 consecutive days. All rats were treated for 3 months. Samples were collected at the end of the treatment period. An Osteocore3 Digital 2D bone densitometer was used to test the bone mineral density, and histomorphometric analysis was performed to measure bone mass, bone formation, and bone resorption. Enzyme-linked immunosorbent assay analysis was used to measure the serum concentrations of interleukin-6 (IL-6), osteoprotegerin (OPG), and receptor activator of nuclear factor-kappa B ligand (RANKL). Immunohistochemistry and in situ hybridization were performed to detect the protein and mRNA expressions of OPG and RANKL in osteoblasts and bone marrow stromal cells.</p></div><div><h3>RESULTS</h3><p>Compared with the OVX group, the esculetin group had significantly greater femoral bone mineral density and tibial trabecular bone volume, and significantly smaller trabecular resorption surface. The percentage of trabecular formation surface, average osteoid width, trabecular bone mineralization rate, and cortical bone mineralization rate did not significantly differ between groups. Compared with the sham group, the esculetin group had significantly decreased serum levels of IL-6 and RANKL, and significant downregulation of RANKL protein and mRNA expression levels in osteoblasts and bone marrow stromal cells; however, there was no significant difference between groups in OPG.</p></div><div><h3>CONCLUSION</h3><p>Esculetin can increase bone mass by upregulating RANKL expression in osteoblasts and bone marrow stromal cells, and decreasing serum IL-6 concentration. This indicates that the therapeutic effect of esculetin on osteoporosis occurs <em>via</em> decreased bone resorption.</p></div>","PeriodicalId":17513,"journal":{"name":"Journal of Traditional Chinese Medicine","volume":"38 6","pages":"Pages 896-903"},"PeriodicalIF":2.0000,"publicationDate":"2018-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0254-6272(18)30989-0","citationCount":"4","resultStr":"{\"title\":\"Effect of esculetin on bone metabolism in ovariectomized rats\",\"authors\":\"Liu Meijie , Wang Ruihai , Li Yan , Bai Dong , Pan Jinghua , Liu Hong , Wang Shaojun , Wu Jiaying , Sun Gang , Miao Qing , Ju Dahong , Liu Limei\",\"doi\":\"10.1016/S0254-6272(18)30989-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>OBJECTIVE</h3><p>To determine the effect of an esculetin formulation (at 97.4% purity) on osteoporosis, and to investigate the potential underlying molecular mechanism(s).</p></div><div><h3>METHODS</h3><p>Sixty specific pathogen free-grade female Wistar rats were randomly assigned to three groups: blank control (<em>n =</em> 12), sham (<em>n =</em> 12), and model (<em>n =</em> 36). The model group were bilaterally ovariectomized. The sham group had the tissue surrounding the ovaries removed, while the ovaries were retained. After 3 months, the model group was randomly divided into three subgroups: OVX (<em>n =</em> 12), positive control (<em>n =</em> 12), and esculetin (<em>n =</em> 12). The positive control group and the esculetin group were intragastrically administered diethylstilbestrol (0.046 mg • kg<sup>−1</sup> • d<sup>−1</sup>) or esculetin (384 mg • kg<sup>−1</sup> • d<sup>−1</sup>), respectively, once per day for 6 consecutive days; medication administration was then stopped for 1 d, before being administered for another 6 consecutive days. All rats were treated for 3 months. Samples were collected at the end of the treatment period. An Osteocore3 Digital 2D bone densitometer was used to test the bone mineral density, and histomorphometric analysis was performed to measure bone mass, bone formation, and bone resorption. Enzyme-linked immunosorbent assay analysis was used to measure the serum concentrations of interleukin-6 (IL-6), osteoprotegerin (OPG), and receptor activator of nuclear factor-kappa B ligand (RANKL). Immunohistochemistry and in situ hybridization were performed to detect the protein and mRNA expressions of OPG and RANKL in osteoblasts and bone marrow stromal cells.</p></div><div><h3>RESULTS</h3><p>Compared with the OVX group, the esculetin group had significantly greater femoral bone mineral density and tibial trabecular bone volume, and significantly smaller trabecular resorption surface. The percentage of trabecular formation surface, average osteoid width, trabecular bone mineralization rate, and cortical bone mineralization rate did not significantly differ between groups. Compared with the sham group, the esculetin group had significantly decreased serum levels of IL-6 and RANKL, and significant downregulation of RANKL protein and mRNA expression levels in osteoblasts and bone marrow stromal cells; however, there was no significant difference between groups in OPG.</p></div><div><h3>CONCLUSION</h3><p>Esculetin can increase bone mass by upregulating RANKL expression in osteoblasts and bone marrow stromal cells, and decreasing serum IL-6 concentration. This indicates that the therapeutic effect of esculetin on osteoporosis occurs <em>via</em> decreased bone resorption.</p></div>\",\"PeriodicalId\":17513,\"journal\":{\"name\":\"Journal of Traditional Chinese Medicine\",\"volume\":\"38 6\",\"pages\":\"Pages 896-903\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2018-12-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S0254-6272(18)30989-0\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Traditional Chinese Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0254627218309890\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Traditional Chinese Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0254627218309890","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
Effect of esculetin on bone metabolism in ovariectomized rats
OBJECTIVE
To determine the effect of an esculetin formulation (at 97.4% purity) on osteoporosis, and to investigate the potential underlying molecular mechanism(s).
METHODS
Sixty specific pathogen free-grade female Wistar rats were randomly assigned to three groups: blank control (n = 12), sham (n = 12), and model (n = 36). The model group were bilaterally ovariectomized. The sham group had the tissue surrounding the ovaries removed, while the ovaries were retained. After 3 months, the model group was randomly divided into three subgroups: OVX (n = 12), positive control (n = 12), and esculetin (n = 12). The positive control group and the esculetin group were intragastrically administered diethylstilbestrol (0.046 mg • kg−1 • d−1) or esculetin (384 mg • kg−1 • d−1), respectively, once per day for 6 consecutive days; medication administration was then stopped for 1 d, before being administered for another 6 consecutive days. All rats were treated for 3 months. Samples were collected at the end of the treatment period. An Osteocore3 Digital 2D bone densitometer was used to test the bone mineral density, and histomorphometric analysis was performed to measure bone mass, bone formation, and bone resorption. Enzyme-linked immunosorbent assay analysis was used to measure the serum concentrations of interleukin-6 (IL-6), osteoprotegerin (OPG), and receptor activator of nuclear factor-kappa B ligand (RANKL). Immunohistochemistry and in situ hybridization were performed to detect the protein and mRNA expressions of OPG and RANKL in osteoblasts and bone marrow stromal cells.
RESULTS
Compared with the OVX group, the esculetin group had significantly greater femoral bone mineral density and tibial trabecular bone volume, and significantly smaller trabecular resorption surface. The percentage of trabecular formation surface, average osteoid width, trabecular bone mineralization rate, and cortical bone mineralization rate did not significantly differ between groups. Compared with the sham group, the esculetin group had significantly decreased serum levels of IL-6 and RANKL, and significant downregulation of RANKL protein and mRNA expression levels in osteoblasts and bone marrow stromal cells; however, there was no significant difference between groups in OPG.
CONCLUSION
Esculetin can increase bone mass by upregulating RANKL expression in osteoblasts and bone marrow stromal cells, and decreasing serum IL-6 concentration. This indicates that the therapeutic effect of esculetin on osteoporosis occurs via decreased bone resorption.
期刊介绍:
Journal of Traditional Chinese Medicine(JTCM) is devoted to clinical and theortical research on the use of acupuncture and Oriental medicine. The main columns include Clinical Observations, Basic Investigations, Reviews, Questions and Answers, an Expert''s Forum, and Discussions of Clinical Cases. Its key topics include acupuncture and electro-acupuncture, herbal medicine, homeopathy, masseotherapy, mind-body therapies, palliative care, and other CAM therapies.