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1.
Poulsen RC Firth EC Rogers CW Moughan PJ Kruger MC 《Calcified tissue international》2007,81(6):459-471
Long chain polyunsaturated fatty acids (LCPUFAs) are involved in the regulation of bone metabolism. Increased dietary consumption
of n-3, and possibly some n-6, LCPUFAs may limit postmenopausal bone loss. The aim of this study was to determine the effects
on bone of specific fatty acids within the n-3 and n-6 LCPUFA families in ovariectomized (OVX) rats. Rats were OVX or sham-operated
and fed either a control diet (OVX and sham) or a diet supplemented with 0.5 g/kg body weight/day of γ-linolenic (GLA), eicosapentaenoic
(EPA), docosahexaenoic (DHA) ethyl esters or a mixture of all three (MIX) for 16 weeks. Bone mineral content (BMC), area,
and density and plasma concentrations of insulin-like growth factor-I, vitamin D, selected biochemical markers of bone metabolism,
and parathyroid hormone (PTH) were determined. The OVX-induced decrease in lumbar spine BMC was significantly attenuated by
DHA but not by EPA or GLA supplementation or supplementation with a mixture of all three LCPUFAs. Endosteal circumferences
of tibiae were significantly greater in DHA and EPA compared to OVX. Plasma C-terminal telopeptide of type I collagen and
osteocalcin concentrations were not significantly different in the DHA group compared to OVX. Femur BMC decreased by a significantly
greater amount in GLA than OVX, and final plasma PTH concentrations were significantly higher in GLA compared to all other
groups. In conclusion, DHA ameliorated OVX-induced bone mineral loss. GLA exacerbated post-OVX bone mineral loss, possibly
as a result of PTH-induced bone catabolism. 相似文献
2.
H M Aukema M R Ogborn K Tomobe H Takahashi T Hibino B J Holub 《Kidney international》1992,42(4):837-842
A paucity of research data exists on the potential for early dietary modification to directly retard cystic growth and proliferation in polycystic kidney disease (PKD). We have therefore examined the relative effects of dietary protein levels and oil type on the progression of disease in a murine model of PKD. In the first study, weanling DBA/2FG-pcy (pcy) mice were fed either a normal (NP), 25%, or low (LP), 6%, casein diet with 10% of either sunflower seed oil (SO) (containing n-6 fatty acids), or fish oil (FO) (containing n-3 fatty acids), in a 2 x 2 design. At the end of the dietary treatment, kidney weight relative to body weight was higher in mice on the NP diets. In addition, kidney phospholipid to kidney weight (mumol/g) was lower in pcy mice on NP diets, indicating that the increased kidney size was largely due to increased cyst development. Replacement of dietary SO with FO resulted in alterations in renal phospholipid fatty acid compositions: 18:2 n-6, 20:4 n-6, and 22:5 n-6 were lower, and 20:5 n-3, 22:5 n-3, and 22:6 n-3 were higher in FO-fed animals. No effect of dietary lipid type on disease progression was noted, however. In a second study, morphometric analysis revealed an 11% lower percentage cyst area and a 46% lower total cyst area (mm2) in kidney sections derived from mice on LP diets compared to NP diets. These results indicate that early dietary protein restriction in PKD prior to clinical manifestation of symptoms of the disease may have a significant impact on the pathogenesis of PKD. 相似文献
3.
Dominique D Pierroz Anna Rufo Estelle N Bianchi Vaida Glatt Mattia Capulli Nadia Rucci Fanny Cavat René Rizzoli Anna Teti Mary L Bouxsein Serge L Ferrari 《Journal of bone and mineral research》2009,24(5):775-784
PTH‐stimulated intracellular signaling is regulated by the cytoplasmic adaptor molecule β‐arrestin. We reported that the response of cancellous bone to intermittent PTH is reduced in β‐arrestin2?/? mice and suggested that β‐arrestins could influence the bone mineral balance by controlling RANKL and osteoprotegerin (OPG) gene expression. Here, we study the role of β‐arrestin2 on the in vitro development and activity of bone marrow (BM) osteoclasts (OCs) and Ephrins ligand (Efn), and receptor (Eph) mRNA levels in bone in response to PTH and the changes of bone microarchitecture in wildtype (WT) and β‐arrestin2?/? mice in models of bone remodeling: a low calcium diet (LoCa) and ovariectomy (OVX). The number of PTH‐stimulated OCs was higher in BM cultures from β‐arrestin2?/? compared with WT, because of a higher RANKL/OPG mRNA and protein ratio, without directly influencing osteoclast activity. In vivo, high PTH levels induced by LoCa led to greater changes in TRACP5b levels in β‐arrestin2?/? compared with WT. LoCa caused a loss of BMD and bone microarchitecture, which was most prominent in β‐arrestin2?/?. PTH downregulated Efn and Eph genes in β‐arrestin2?/?, but not WT. After OVX, vertebral trabecular bone volume fraction and trabecular number were lower in β‐arrestin2?/? compared with WT. Histomorphometry showed that OC number was higher in OVX‐β‐arrestin2?/? compared with WT. These results indicate that β‐arrestin2 inhibits osteoclastogenesis in vitro, which resulted in decreased bone resorption in vivo by regulating RANKL/OPG production and ephrins mRNAs. As such, β‐arrestins should be considered an important mechanism for the control of bone remodeling in response to PTH and estrogen deprivation. 相似文献
4.
Vitamin D hormone inhibits osteoclastogenesis in vivo by decreasing the pool of osteoclast precursors in bone marrow. 总被引:4,自引:0,他引:4
Takeshi Shibata Ayako Shira-Ishi Takuya Sato Toshimi Masaki AyaSasakiYoshiko Masuda Akinori Hishiya Nobuyuki Ishikura Sayumi Higashi Yasuhiro Uchida Moto-O Saito Masako Ito Etsuro Ogata Ken Watanabe Kyoji Ikeda 《Journal of bone and mineral research》2002,17(4):622-629
Previous observations that vitamin D hormone induces the expression of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL), thereby stimulating osteoclastogenesis in vitro, led to the widespread belief that 1alpha,25-dihydroxyvitamin D3 [1a,25(OH)2D3] is a bone-resorbing hormone. Here, we show that alfacalcidol, a prodrug metabolized to 1alpha,25(OH)2D3, suppresses bone resorption at pharmacologic doses that maintain normocalcemia in an ovariectomized (OVX) mouse model of osteoporosis. Treatment of OVX mice with pharmacologic doses of alfacalcidol does not increase RANKL expression, whereas toxic doses that cause hypercalcemia markedly reduce the expression of RANKL. When bone marrow (BM) cells from OVX mice were cultured with sufficient amounts of macrophage colony-stimulating factor (M-CSF) and RANKL, osteoclastogenic activity was higher than in sham mice. Marrow cultures from alfacalcidol- or estrogen-treated OVX mice showed significantly less osteoclastogenic potential compared with those from vehicle-treated OVX mice, suggesting that the pool of osteoclast progenitors in the marrow of vitamin D-treated mice as well as estrogen-treated mice was decreased. Frequency analysis showed that the number of osteoclast progenitors in bone marrow was increased by OVX and decreased by in vivo treatment with alfacalcidol or estrogen. We conclude that the pharmacologic action of active vitamin D in vivo is to decrease the pool of osteoclast progenitors in BM, thereby inhibiting bone resorption. Because of its unusual activity of maintaining bone formation while suppressing bone resorption, in contrast to estrogens that depress both processes, vitamin D hormone and its bone-selective analogs may be useful for the management of osteoporosis. 相似文献
5.
Karina L Nielsen Matthew R Allen Susan A Bloomfield Thomas L Andersen Xiao-Dong Chen Hans S Poulsen Marian F Young Anne-Marie Heegaard 《Journal of bone and mineral research》2003,18(12):2152-2158
Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4-week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss and that there is a gender difference in the response to biglycan deficiency. INTRODUCTION: Biglycan (bgn) is a small extracellular matrix proteoglycan enriched in skeletal tissues, and biglycan-deficient male mice have decreased trabecular bone mass and bone strength. The purpose of this study was to investigate the bone phenotype of the biglycan-deficient female mice and to investigate the effect of estrogen depletion by ovariectomy (OVX). MATERIALS AND METHODS: OVX or sham operations were performed on 21-week-old mice that were divided into four groups: wt sham (n = 7), wt OVX (n = 9), bgn-deficient sham (n = 10) and bgn-deficient OVX (n = 10). The mice were killed 4 weeks after surgery. Bone mass and bone turnover were analyzed by peripheral quantitative computed tomography (pQCT), biochemical markers, and histomorphometry. RESULTS AND CONCLUSIONS: In contrast to the male mice, there were only few effects of bgn deficiency on bone metabolism in female mice, showing a clear gender difference. However, when stressed by OVX, the female bgn knockout (KO) mice were resistant to the OVX-induced trabecular bone loss. The wt mice showed a decrease in trabecular bone mineral density by pQCT measurements, a decrease in trabecular bone volume (BV/TV), and an increase in mineral apposition rate. In contrast, no significant changes were detected in bgn KO mice after OVX. In addition, analysis of the bone resorption marker deoxypyridinoline showed no significant increase in the bgn KO OVX mice compared with bgn KO sham mice. Measurements of serum osteoprotegerin (OPG) and RANKL revealed increased levels of OPG and decreased levels of RANKL in the bgn KO mice compared with wt mice. In conclusion, the bgn deficiency protects against increased trabecular bone turnover and bone loss in response to estrogen depletion, supporting the concept that bgn has dual roles in bone, where it may modulate both formation and resorption ultimately influencing the bone turnover process. 相似文献
6.
Yoshiya Tomimori Kaoru Mori Masanori Koide Yuko Nakamichi Tadashi Ninomiya Nobuyuki Udagawa Hisataka Yasuda 《Journal of bone and mineral research》2009,24(7):1194-1205
Osteoporosis remains a major public health problem through its associated fragility fractures. Several animal models for the study of osteoporotic bone loss, such as ovariectomy (OVX) and denervation, require surgical skills and several weeks to establish. Osteoclast differentiation and activation is mediated by RANKL. Here we report the establishment of a novel and rapid bone loss model by the administration of soluble RANKL (sRANKL) to mice. Mice were injected intraperitoneally with sRANKL and used to evaluate existing anti‐osteoporosis drugs. sRANKL decreased BMD within 50 h in a dose‐dependent manner. The marked decrease in femoral trabecular BMD shown by pQCT and the 3D images obtained by μCT were indistinguishable from those observed in the OVX model. Histomorphometry showed that osteoclastic activity was significantly increased in the sRANKL‐injected mice. In addition, serum biochemical markers of bone turnover such as Ca, C‐telopeptide of type 1 collagen (CTX), and TRACP5b were also significantly increased in the sRANKL‐injected mice in a dose‐dependent manner. Bisphosphonates (BPs), selective estrogen receptor modulators (SERMs), and PTH are commonly used for the treatment of osteoporosis. We successfully evaluated the effects of anti–bone‐resorbing agents such as BPs, a SERM, and anti–RANKL‐neutralizing antibody on bone resorption in a couple of weeks. We also evaluated the effects of PTH on bone formation in 2 wk. A combination of sRANKL injections and OVX made it possible to evaluate a SERM. The sRANKL model is the simplest, fastest, and easiest of all osteoporosis models and could be useful in the evaluation of drug candidates for osteoporosis. 相似文献
7.
目的 以雌二醇为对照,观察二甲双胍(metformin, MF)对去卵巢大鼠骨密度及骨矿含量的影响,并从细胞、分子水平探究MF可能的骨保护机制。方法 将60只雌性SD大鼠随机均分4组:假手术(SHAM)组、去卵巢(OVX)组、去卵巢+二甲双胍(OVX+MF)组和去卵巢+雌二醇(OVX+E2 )组。分组灌胃给药60 d后测量大鼠右侧胫骨骨密度和骨矿含量;分离培养各组大鼠骨髓间充质干细胞(BMSCs)并诱导其向成骨细胞分化,用MTT法测定细胞活性及增殖能力;测定各组碱性磷酸酶(ALP)活性、矿化结节数目、钙含量以及I型胶原(collagen type I)、骨钙素(OC)、骨保护素 (OPG)、NFκB受体的配体 (RANKL)、白细胞介素-6(IL-6)基因表达水平。结果 与OVX组相比,OVX+MF组和OVX+E2组成骨细胞的增殖能力与ALP活性明显增强,骨密度、骨矿含量以及钙沉积量显著增加(P均<0.05),且两组collagen type I、OC、OPG mRNA的表达水平显著升高,而RANKL、IL-6mRNA表达明显受到抑制;但OVX+MF组去卵巢大鼠成骨细胞的增殖能力、ALP活性、钙沉积量、collagen type I、OC、OPG mRNA表达水平低于OVX+E2组,RANKL、IL-6mRNA表达高于OVX+E2组(P均<0.05);与SHAM组比较,OVX+MF组的collagen type I、OC、OPG mRNA的表达水平更高(P<0.05)。结论 二甲双胍可能通过OPG/RANKL/RANK信号通路促进BMSCs向成骨细胞分化,有效逆转去卵巢大鼠骨质疏松的状态,这种潜在的骨保护作用可能会改善糖尿病引起的骨质疏松。 相似文献
8.
目的探讨虾青素能否防治去卵巢糖尿病大鼠的骨质流失以及可能的机制。方法 3月龄雌性SD大鼠分为3组(每组6只):对照组CON(假手术),模型组OVX/T1DM(去卵巢糖尿病大鼠),药物组OVX/T1DM-ASX(去卵巢糖尿病大鼠,给予虾青素100 mg/(kg·d)。结果连续治疗60 d后,与OVX/T1DM组相比,OVX/T1DM-ASX组骨密度(BMD)明显升高(P0.01),血清I型胶原蛋白(CTX-1)、骨钙素、I型前胶原蛋白n端前肽(PINP)、抗酒石酸磷酸酶5b(TRACP 5b)水平均显著升高(P0.01)。虾青素治疗能抑制去卵巢糖尿病大鼠骨组织形态学的改变,减少骨髓脂肪细胞增加,提高OPG/RANKL的比值。结论虾青素对绝经后糖尿病骨质流失有保护作用,这种作用与调控OPG/RANKL轴有关。 相似文献
9.
Sun-Kyeong Lee Judith F Kalinowski Claire Jacquin Douglas J Adams Gloria Gronowicz Joseph A Lorenzo 《Journal of bone and mineral research》2006,21(5):695-702
IL-7 is produced by stromal cells in bone marrow and is a major regulator of B and T lymphopoiesis. It is also a direct inhibitor of osteoclastogenesis in vitro. In this study we show that IL-7-deficient mice have increased OC and decreased trabecular bone volume compared with WT mice but mimic WT mice in the amount of trabecular but not cortical bone lost after ovariectomy. INTRODUCTION: Interleukin (IL)-7 is a potent regulator of lymphocyte development, which has significant effects on bone. Bone marrow cell cultures from IL-7 deficient (IL-7KO) mice produced significantly more TRACP(+) osteoclasts (OCs) than did cells from wildtype (WT) mice. A previous study found that treatment of mice with a neutralizing antibody to IL-7 blocked ovariectomy (OVX)-induced bone loss. We examined if differences exist between the bones of WT and IL-7KO mice and if OVX altered bone mass in IL-7KO mice. MATERIALS AND METHODS: Studies were in 2-month-old sham-operated (SHAM) and OVX female mice that were killed 4 weeks after surgery. IL-7KO mice and WT controls were in a C57BL/6 background. Both vertebrae (L(1)) and femora were evaluated by DXA, muCT, and histomorphometry. IL-7KO mice were confirmed as IL-7 deficient by their almost total lack of mature B cells in their bone marrow. RESULTS: There was significantly less trabecular bone volume in the vertebrae of IL-7KO mice than in WT mice. In addition, IL-7KO mice had significantly decreased (p < 0.05) trabecular number (13%) and increased trabecular spacing (15%). OVX decreased vertebral trabecular bone volume (TBV) by 21% (p < 0.05) in WT mice and by 22% (p < 0.05) in IL-7KO mice compared with SHAM. IL-7KO SHAM mice also had significantly less (30%) TBV (TA/TTA) in their femurs, as measured histomorphometrically, than did WT SHAM mice. Femurs from IL-7KO SHAM mice had significantly increased percent OC surface (23%) compared with WT SHAM. As in the vertebrae, OVX significantly decreased femoral TBV in both WT and IL-7KO mice by similar amounts (47% and 48%, respectively, p < 0.05 for both) compared with SHAM. However, OVX decreased cortical bone mass in WT but not in IL-7KO bones. We also examined bone marrow cells from WT and IL-7KO mice. Bone marrow cells from IL-7KO animals showed a significant increase in the number of TRACP(+) osteoclast-like cells (OCLs), which formed in cultures that were stimulated with macrophage-colony stimulating factor (M-CSF) and RANKL (both at 30 ng/ml). However, there was no significant difference in the number of OCLs that formed in B lymphocyte-depleted (B220(-)) bone marrow cell cultures from WT and IL-7KO mice. CONCLUSIONS: IL-7 deficiency in mice caused increased OC number in bone and decreased bone mass. OVX-induced bone loss in IL-7-deficient mice was selective and occurred in trabecular but not cortical bone. 相似文献
10.
Roxana Begum Martha A Belury John R Burgess Louise W Peck 《Journal of renal nutrition》2004,14(4):233-241
OBJECTIVE: To investigate the effect of supplementation with different sources of oils rich in long chain fatty acids, ie, fish oil (FO) and safflower oil (SO), on the production of leukotriene B4 (LTB4) by polymorphonuclear leukocytes (PMNLs) in hemodialysis patients and the consequent effects on the symptoms of pruritus. DESIGN: Randomized, prospective, double-blind study for 2 treatment groups. SETTING: Three Medical Center-affiliated units. PATIENTS: Twenty-two patients on maintenance hemodialysis, of both sexes, age > or = 20 years with complaint of dry and/or itchy skin. INTERVENTION: Two groups of patients receiving daily supplements of 6 g ethyl ester of FO or SO for 16 weeks. MAIN OUTCOME MEASURES: Red blood cell (RBC) fatty acid profile, LTB 4 production by PMNLs, and pruritus symptoms at baseline and after supplementation. RESULTS: After supplementation, the FO group had a higher RBC 22:6n3, total n-3 fatty acids, and ratio of total n-3 to total n-6 fatty acids (P < .05) than the SO group. The change in LTB4 production (pg/mL) from baseline to week 16 was 240.7 +/- 200.2 to 29.2 +/- 14.6 in the FO group and from 171.1 +/- 121.7 to 31.9 +/- 14.7 in the SO group. The overall pruritus score change was 16.7 +/- 11.4 to 8.9 +/- 9.2 in the FO group and from 17.5 +/- 8.8 to 13.1 +/- 5.6 in the SO group. FO supplementation did not result in a significant specific effect on LTB4 production by the PMNLs. There was a nonsignificant decrease in the pruritus scores that could be clinically significant and important to patients suffering with this condition. CONCLUSION: Supplementation with FO results in significant incorporation of n-3 fatty acids in the RBCs. Intervention with both FO and SO resulted in a nonsignificant improvement of clinical symptoms of pruritus and a nonsignificant reduction in LTB 4 production by PMNLs in the hemodialysis patients. The percent decrease in total puritus score was greater for the FO group compared with the SO group. 相似文献
11.
Improved survival of heterotopic cardiac allografts in rats with dietary n-3 polyunsaturated fatty acids 总被引:3,自引:0,他引:3
A heterotopic cardiac transplant model, with male Fischer 344 rats as donors and Long Evans rats as recipients, was utilized to investigate the effect of dietary n-3 polyunsaturated fatty acids on acute rejection. Both donor and recipient rats were fed purified diets high in either n-3 polyunsaturated fatty acids (from concentrated n-3 ethyl esters [EE] or fish oil [FO]) or n-6 polyunsaturated fatty acids (from corn oil [CO]) for either 2-3 or 3-4 weeks before transplant. The recipient rats continued on their diets until rejection. The AIN-76A-based diets (with 30% of calories as fat) had adequate essential fatty acids and were balanced for sterols and antioxidants. Allograft survival was significantly increased by 45% when recipient rats were fed EE as compared to the control (CO diet fed to both donor and recipient), regardless of the diet fed to the donor. There was a slight but significant increase in allograft survival when only donor rats were fed the EE diet 2-3 weeks before transplant. With the FO diet (containing one third of the n-3 fatty acids in the EE diet), only the group fed FO to both donor and recipient (starting 2-3 weeks before transplant) showed a significant increase in allograft survival over the control. However, if the FO diets were fed for 3-4 weeks before transplant, increased survival was seen in groups fed FO to either the donor or recipient alone. In this case, allograft survival with FO feeding to both donor and recipient was not different from recipient treatment alone. In all the studies there was a significant and direct correlation between allograft survival and the donor heart phospholipid n-3/n-6 fatty acid ratio and the n-3 fatty acid content (at rejection). There was an indirect relationship with the n-6 fatty acid content. There was no detectable 20:3 (n-9) in the cardiac phospholipids, indicating the absence of essential fatty acid deficiency. Recipient diets were the strongest determinant of the fatty acid composition in the transplanted donor heart. The data indicate that providing dietary n-3 polyunsaturated fatty acids before and after cardiac transplant to recipient animals provides a significant protection against acute rejection. 相似文献
12.
Purpose: To study the effects of estrogen withdrawal on osteoclast number and osteoclast activity in the rat ovariectomy (OVX) model.
Methods: We first cultured human CD34+ osteoclast precursor cells on bovine bone slices, allowing them to differentiate into mature
resorbing osteoclasts. Secreted tartrate-resistant acid phosphatase 5b (TRACP 5b) and C-terminal cross-linked telopeptides
of type I collagen (CTX) were determined from the culture medium. TRACP 5b correlated strongly with osteoclast number and
CTX with osteoclast activity, facilitating their subsequent use in the rat OVX model. An 8 week OVX study was then performed
including sham-operated rats receiving vehicle, OVX rats receiving vehicle, and OVX rats receiving 10 μg/kg/day 17β-estradiol
(E2). Trabecular bone parameters were determined from the tibial metaphysis using peripheral quantitative computed tomography
and histomorphometry. Osteoclast number was normalized with bone perimeter (N.Oc/B.Pm) and tissue area (N.Oc/T.Ar, indicating
absolute number of osteoclasts). TRACP 5b and CTX were determined from fasting serum samples.
Results: Trabecular bone parameters indicated substantial bone loss after OVX that was prevented by E2. N.Oc/B.Pm increased after OVX,
while N.Oc/T.Ar and TRACP 5b decreased, and TRACP 5b correlated strongly with N.Oc/T.Ar. However, CTX values increased after
OVX, and the “resorption index” CTX/TRACP 5b showed more substantial changes than either CTX or TRACP 5b alone.
Conclusion: These results show that TRACP 5b is a reliable marker of osteoclast number, and the index CTX/TRACP 5b is a useful parameter
in rat OVX model. The high elevation of CTX/TRACP 5b values by OVX demonstrates that estrogen withdrawal generates high activity
of osteoclasts in the rat OVX model.
Disclosure statement: Jukka Rissanen, Mari Suominen, and Zhiqi Peng have nothing to disclose; Jussi Halleen receives royalties
from and works as a consultant of SBA Sciences, a company owned by IDS Ltd. 相似文献
13.
Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) consumption has been reported to improve bone health. However, sources of ω-3 PUFAs differ in the type of fatty acids and structural form. The study objective was to determine the effect of various ω-3 PUFAs sources on bone during growth. Young (age 28d) female Sprague-Dawley rats were randomly assigned (n=10/group) to a high fat 12% (wt) diet consisting of either corn oil (CO) or ω-3 PUFA rich, flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) for 8 weeks. Bone mass was assessed by dual-energy X-ray absorptiometry (DXA) and bone microarchitecture by micro-computed tomography (μCT). Bone turnover markers were measured by enzyme immunoassay. Lipid peroxidation was measured by calorimetric assays. Results showed that rats fed TO, rich in docosahexaenoic acid (DHA, 22:6ω-3) had higher (P<0.009) tibial bone mineral density (BMD) and bone mineral content (BMC) and lower (P=0.05) lipid peroxidation compared to the CO-fed rats. Reduced lipid peroxidation was associated with increased tibial BMD (r2=0.08, P=0.02) and BMC (r2=0.71, P=0.01). On the other hand, rats fed FO or MO, rich in alpha-linolenic acid (ALA, 18:3ω-3), improved bone microarchitecture compared to rats fed CO or SO. Serum osteocalcin was higher (P=0.03) in rats fed FO compared to rats fed SO. Serum osteocalcin was associated with improved trabecular bone microarchitecture. The animal study results suggest consuming a variety of ω-3 PUFA sources to promote bone health during the growth stage. 相似文献
14.
Lindberg MK Svensson J Venken K Chavoshi T Andersson N Movérare Skrtic S Isaksson O Vanderschueren D Carlsten H Ohlsson C 《BONE》2006,38(1):85-92
INTRODUCTION: Estrogen deficiency results in trabecular bone loss, associated with T-cell proliferation in the bone marrow. Insulin-like growth factor I (IGF-I) is involved in the regulation of both bone metabolism and lymphopoiesis. A major part of serum IGF-I is derived from the liver. The aim of the present study was to investigate the role of liver-derived IGF-I for ovariectomy (ovx)-induced trabecular bone loss. MATERIALS AND METHODS: Mice with adult liver-specific IGF-I inactivation (LI-IGF-I-/-) and wild type mice (WT) were either ovx or sham operated. After 5 weeks, the skeletal phenotype was analyzed by pQCT and microCT. The bone marrow cellularity was analyzed using FACS technique, and mRNA levels were quantified using real-time PCR. RESULTS: Ovx resulted in a pronounced reduction in trabecular bone mineral density (-52%, P < 0.001), number (-45%, P < 0.01) and thickness (-13%, P < 0.01) in WT mice while these bone parameters were unaffected by ovx in LI-IGF-I-/- mice. Furthermore, ovx increased the number of T-cells in the bone marrow of the femur in WT but not in LI-IGF-I-/- mice. Interleukin 7 (IL-7) has been reported to stimulate the formation and function of osteoclasts by inducing the expression of receptor activator of NF-kappaB ligand (RANKL) on T-cells. IL-7 mRNA levels and the RANKL/osteoprotegerin ratio in bone were increased by ovx in WT but not in LI-IGF-I-/- mice. CONCLUSIONS: Liver-derived IGF-I is permissive for ovx-induced trabecular bone loss. Our studies indicate that IGF-I might exert this permissive action by modulation of the number of T-cells and the expression of IL-7, which in turn is of importance for the RANKL/OPG ratio and consequently osteoclastogenesis in the bone marrow. 相似文献
15.
Magnesium (Mg) deficiency has been reported to result in increases in bone resorption through changes in the cytokine system,
such as decreases in serum osteoprotegerin (OPG) concentrations and increases in receptor activator of NF-κB ligand (RANKL)
concentrations. However, there are few data about the effects of Mg supplementation on OPG and RANKL. This study was carried
out to investigate the effects of Mg supplementation on bone mineral density (BMD), bone mineral content (BMC), serum OPG,
and RANKL in ovariectomized (OVX) rats relative to calcium (Ca) intake levels. Fifty-five Sprague-Dawley female rats were
divided into the following five groups and fed for 12 weeks as indicated: sham-operated control group (sham), OVX Ca-deficient
group (OLCa, 0.1% Ca and 0.05% Mg), OVX Ca-deficient and Mg-supplemented group (OLCaMg, 0.1% Ca and 0.1% Mg), OVX Ca-adequate
group (OACa, 0.5% Ca and 0.05% Mg), and OVX Ca-adequate and Mg-supplemented group (OACaMg, 0.5% Ca and 0.1% Mg). The BMD of
the lumbar spine, femur, and tibia in the OVX groups was significantly lower than that in the sham group. The OVX group with
an adequate-Ca diet showed significantly higher BMC of the lumbar spine compared to the low Ca–diet group regardless of Mg
supplementation. The OACaMg group had significantly higher levels of OPG and OPG/RANKL ratio than did the OLCa group. From
the above results, it is still unclear whether Mg supplementation can improve bone mineral status, while Mg supplementation
with an adequate-Ca diet resulted in a change in cytokines that may promote bone formation. 相似文献
16.
Uchida R Chiba H Ishimi Y Uehara M Suzuki K Kim H Matsumoto A 《Journal of bone and mineral metabolism》2011,29(4):404-413
Both soy isoflavone and n-3 polyunsaturated fatty acids are known to reduce the levels of bone-resorbing cytokines; however,
the synergistic effects of these food ingredients have not been examined yet. This study was performed to elucidate the effect
of concomitant intake of soy isoflavone and fish oil on bone mass in ovariectomized mice. Eight-week-old ddY female mice were
subjected to ovariectomy (OVX) or sham surgery, and then fed an AIN-93G with safflower oil (So) as a control lipid source,
isoflavone-supplemented safflower oil (So + I), fish oil instead of safflower oil (Fo) or isoflavone-supplemented fish oil
(Fo + I) for 4 weeks. Femoral bone mineral density was significantly decreased by OVX; however, this decrease was inhibited
by the intake of isoflavone and/or fish oil. Histomorphometric analyses showed that bone volume and trabecular thickness in
the distal femoral trabecular bone were significantly lower in the So group than in the sham group, but those were restored
in the Fo + I groups. The number of osteoclasts was significantly decreased by isoflavone intake. The increased rate of bone
resorption after OVX was inhibited by isoflavone and/or fish oil. The serum concentration of tumor necrosis factor alpha was
increased after OVX, but was significantly lower with the combination of isoflavone with fish oil than isoflavone or fish
oil alone. The results of this study indicated that the intakes of soy isoflavone and/or fish oil might have ameliorating
effects on bone loss due to OVX. Further, the concomitant intake of soy isoflavone and fish oil at a low dose showed better
effects on cytokines related with bone resorption. 相似文献
17.
核因子与白细胞介素-6在骨质疏松模型中的表达特征 总被引:2,自引:0,他引:2
目的 探讨白细胞介素(IL)-6和核因子变化对绝经后骨质疏松的影响,以及其在骨质疏松发病过程中的关系及意义。方法 4月龄成年雌性BALB/C小鼠随机分假手术对照组和去卵巢骨质疏松模型组,术后第12周测量全身骨密度后处死,用免疫组织化学方法测定股骨下端骨组织中核因子及IL-6的蛋白含量及表达水平并进行细胞定位,对照研究骨密度(BMD)和骨微环境中核因子及IL-6水平。结果 去卵巢骨质疏松模型组小鼠与假手术对照组相比,骨密度下降,骨小梁稀疏;免疫组织化学染色结果显示。核因子及IL-6蛋白在模型组蛋白含量明显高于对照组且与骨密度呈显著负相关(P<0.01或P<0.05),NF-kB p65与IL-6呈显著正相关(P<0.01)。结论 绝经后骨质疏松症骨组织及骨髓中核因子的蛋白含量及表达水平升高。可能激活破骨细胞分化因子IL-6的转录,使其表达增加,骨吸收活动增强,造成骨组织形态改变并导致骨质疏松。 相似文献
18.
19.
Christian Wedemeyer Carl Neuerburg Anne Pfeiffer Anja Heckelei David Bylski Fabian von Knoch Thorsten Schinke Gero Hilken Georg Gosheger Marius von Knoch Franz L?er Guido Saxler 《Journal of bone and mineral research》2007,22(7):1011-1019
This study investigates the impact of alpha-CGRP on bone metabolism after implantation of polyethylene particles. alpha-CGRP knockout mice showed less osteolysis compared with wildtype mice. The local neurogenic microenvironment might be a crucial factor in particle-induced osteolysis. INTRODUCTION: Periprosthetic osteolysis is the major reason for aseptic loosening in joint arthroplasty. This study aimed to investigate the potential impact of alpha-calcitonin gene-related peptide (alpha-CGRP) deficiency on bone metabolism under conditions of polyethylene particle-induced osteolysis. MATERIALS AND METHODS: We used the murine calvarial osteolysis model based on polyethylene particles in 14 C57BL 6 mice and 14 alpha-CGRP-deficient mice divided into four groups of 7 mice each. Groups 1 (C57BL/J 6) and 3 (alpha-CGRP knockout) received sham surgery, and groups 2 (C57BL/J 6) and 4 (alpha-CGRP knockout) were treated with polyethylene particles. Qualitative and quantitative 3D analyses were performed using microCT. In addition, bone resorption was measured within the midline suture by histological examination. The number of osteoclasts was determined by counting the TRACP(+) cells. Calvarial bone was tested for RANKL expression by RT-PCR and immunocytochemistry. RESULTS: Bone resorption was significantly reduced in alpha-CGRP-deficient mice compared with their corresponding wildtype C57BL 6 mice as confirmed by histomorphometric data (p < 0.001) and microCT (p < 0.01). Osteoclast numbers were significantly reduced in group 3 and the particle subgroup compared with group 1 (p < 0.001). We observed a >3-fold increase of basal RANKL mRNA levels within group 1 compared with group 3. Additional low RANKL immunochemistry staining was noted in groups 3 and 4. CONCLUSIONS: In conclusion, alpha-CGRP knockout mice did not show the expected extended osteolysis compared with wildtype mice expressing alpha-CGRP. One of the most reasonable explanations for the observed decrease in osteolysis could be linked to the osteoprotegerin (OPG)/RANK/RANKL system in alpha-CGRP-deficient animals. As a consequence, the fine tuning of osteoclasts mediating resorption in alpha-CGRP-null mice may be deregulated. 相似文献
20.
目的观察培本固疏方对去卵巢骨质疏松模型大鼠骨密度、骨生物力学及骨代谢指标的影响。方法将42只SD大鼠随机分为假手术组(SHAM)、模型对照组(OVX)、中药低剂量组(D)、中药中剂量组(Z)、中药高剂量组(G)和西药组(X),通过切除大鼠双侧卵巢建立骨质疏松症模型,假手术组仅切除卵巢周围约1 g的脂肪组织。造模4周后进行药物干预,各组持续灌胃8周。计算子宫指数,测定股骨骨密度(bone mineral density,BMD)及股骨生物力学弹性载荷、极限载荷、弹性模量等指标;采用ELISA法测定血清骨代谢指标TRACP5b、sRANKL、OPG及氧化应激指标MDA、AGEs的含量。结果与SHAM组比较,OVX组子宫指数、股骨近端和股骨中段BMD、弹性载荷、弹性模量均明显降低(P0. 05),OVX组血清MDA、AGEs含量明显升高(P0. 01),血清TRACP5b含量明显升高(P0. 01),而OPG、OPG/sRANKL比值下降(P0. 01);与OVX组相比,各治疗组子宫指数、骨强度均有所改善。Z组、G组及X组BMD均明显增高(P0. 05)。Z组、G组及X组TRACP5b含量下降(P0. 05)、OPG含量升高(P0. 05)、RANKL含量降低、OPG/sRANKL比值升高(P0. 05)。Z组、G组血清MDA、AGEs含量降低(P0. 05)。结论培本固疏方可以增加骨强度,通过OPG/RANKL/RANK通路来抑制破骨细胞形成,减缓骨基质吸收,抗氧化应激机制也可能参与其中,具体机制有待探讨。 相似文献