依普黄酮对骨质疏松症笼养蛋鸡OPG和RANKL表达的影响

选用200只24周龄健康海兰褐蛋鸡,随机分为4组:对照组(基础日粮中含钙3.55％)、低钙组(日粮合钙1.27％)、试验Ⅰ组(依普黄酮8 mg/kg,低钙日粮)和试验Ⅱ组(依普黄酮20 mg/kg,低钙日粮),观察依普黄酮对骨质疏松症笼养蛋鸡血清及骨骼骨保护素(Osteo protegerin,OPG)/核因子-相受体活化因子配体(Receptor activatorof NF-κB ligand,RANKL)表达的影响.结果显示:与低钙组相比,30 d时,试验Ⅰ组和Ⅱ组血清OPG分别显著升高33.12％和60.19％(P＜0.05)；60 d时,试验Ⅰ组和Ⅱ组血清OPG分别显著升高35.89％和61.59％ (P＜0.05)；30 d时,试验Ⅰ组和Ⅱ组血清RANKL分别极显著降低63.85％和70.87％(P＜0.01)；60 d时,试验Ⅰ组和Ⅱ组血清RANKL分别极显著降低69.98％和72.85％ (P＜0.01).与低钙组相比,试验Ⅰ组和Ⅱ组骨组织OPG平均光密度分别显著(P＜0.05)和极显著(P＜0.01)升高,试验Ⅰ组和Ⅱ组蛋鸡骨组织RANKL平均光密度极显著低于低钙组蛋鸡(P＜o.01).试验Ⅰ组和Ⅱ组OPG/RANKL值高于低钙组.结果表明,低钙日粮中添加依普黄酮对蛋鸡骨质疏松症可起到一定改善作用,这可能与OPG上调,RANKL下调,影响RANKL信号通路,使其骨量增加,骨结构改善密切相关.     

Placotylene A,an Inhibitor of the Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclast Differentiation,from a Korean Sponge Placospongia sp.

A new inhibitor, placotylene A (1), of the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation, and a regioisomer of placotylene A, placotylene B (2), were isolated from a Korean marine sponge Placospongia sp. The chemical structures of placotylenes A and B were elucidated on the basis of 1D and 2D NMR, along with MS spectral analysis and revealed as an iodinated polyacetylene class of natural products. Placotylene A (1) displayed inhibitory activity against RANKL-induced osteoclast differentiation at 10 μM while placotylene B (2) did not show any significant activity up to 100 μM, respectively.     

Echinacoside promotes bone regeneration by increasing OPG/RANKL ratio in MC3T3-E1 cells

Echinacoside (ECH), isolated from Cistanche tubulosa (Schrenk) R. Wight stems, was subjected to in vitro experiments to investigate its bioactivities on proliferation, differentiation and mineralization of the osteoblastic cell line MC3T3-E1. MTT assay, the alkaline phosphatase (ALP) activity and calcium deposition were determined, and the secretion of collagen I (COL I), osteocalcin (OCN), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were also assayed by enzyme-linked immunosorbent assay (ELISA). The results showed that ECH caused a significant increase in cell proliferation, ALP activity, COL I contents, OCN levels and an enhancement of mineralization in osteoblasts at the concentration range from 0.01 to 10 nmol·L^− 1 (p < 0.05), suggesting that ECH has a stimulatory effect on osteoblastic bone formation or has potential activity against osteoporosis. In addition, the ratio of OPG/RANKL also could be enhanced by ECH. These findings provide the potent evidence that ECH can promote bone regeneration in cultured osteoblastic MC3T3-E1 cells, which might be done by elevating the OPG/RANKL ratio, and potential evidence for echinacoside to be a promising drug or a lead compound in the development of disease-modifying drug to prevent osteoporosis.     

OPG/RANKL/RANK系统的生理功能

骨是一个代谢活跃的器官,在整个生命周期中都在进行不断的更新与重建。在骨形态发生和重建的过程中主要受到细胞因子和激素的调节,同时骨代谢也受到OPG/RANKL/RANK系统的调控。论文主要对骨骼生理结构与骨组织细胞之间的关系,骨代谢和骨的形成过程,OPG/RANKL/RANK系统的生理功能,OPG/RANKL/RANK系统的影响因子以及骨代谢紊乱所引起的疾病几个方面作一综述。     

Dietary phosphorus restriction affects bone metabolism,vitamin D metabolism and rumen fermentation traits in sheep

Homeostasis of calcium (Ca) and phosphate (P_i) is maintained by a concerted interplay of absorption and reabsorption via the gastrointestinal tract and the kidney and by storage and mobilization from the bone regulated mainly by parathyroid hormone (PTH), 1,25-dihydroxycholecalciferol and calcitonin. The present study aimed at characterizing the effects of dietary P restriction on bone, vitamin D metabolism and rumen fermentation traits reflecting the endogenous P cycle maintaining the ruminal P supply for microbial metabolism. The experiments were done in eleven female, non-pregnant, non-lactating four- to nine-year-old Black Headed Mutton sheep allotted to two feeding groups: "P-restricted" (0.11% P/kg DM and 0.88% Ca/kg DM) and "Control" (0.38% P/kg DM and 0.88% Ca/kg DM). Dietary P restriction did not lead to hypophosphataemia, probably due to a compensation by bone mobilization, demonstrated by increased serum concentrations of a resorption marker and altered gene expression in bone tissue. In addition, the RNA expression of fibroblast growth factor 23, a bone-derived factor involved in the regulation of vitamin D metabolism, was significantly reduced with dietary P restriction. Furthermore, several genes related to vitamin D metabolism and plasma concentrations of 1,25-(OH)₂D were associated with serum concentrations of phosphate (P_i). In the parotid gland, the expression of the P_i transporter NaPi2b was negatively associated with serum P_i and positively with parathyroid PTH expression. Although P_i concentrations in saliva and the gastrointestinal tract were significantly reduced, we found no adverse effects of the P-restricted ration on the production of short chain fatty acids, but slight differences in the production of butyrate as well as its relationship to rumen P_i and ammonia concentrations that might indicate an impact on ruminal fermentation.     

The comparative biology of skeletal metastasis

Bone metastasis, a very common sequelae of cancer, is often associated with great morbidity. Understanding the biology of bone metastases may lead to therapeutic interventions to target the metastases. In addition to replacing bone marrow elements, the presence of tumour cells in bone modulates the normal bone remodelling process. Some tumours result in primarily osteolytic bone lesions, whereas others are associated with osteoblastic bone lesions. In either case, the resulting changes in the bone structure result in weakened bone that induces pain and is predisposed to fracture. The mechanisms through which cancer cells modulate bone remodelling are not clearly defined, but ongoing research using a variety of animal models will hopefully provide clues to prevent or slow the progress of bone metastases.     

Impact of Pueraria candollei var. mirifica and its potent phytoestrogen miroestrol on expression of bone-specific genes in ovariectomized mice

Miroestrol (MR) is a highly active phytoestrogen isolated from tuberous root of Pueraria candollei var. mirifica (PM). Modulatory effects of PM and MR on osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) mRNAs which are bone-specific genes were investigated in ovariectomized female ICR mice. After ovariectomy, expression of OPG mRNA was suppressed but that of RANKL was induced. Estradiol benzoate (E2) recovered OPG expression to the level comparable to the sham while that of RANKL was suppressed in ovariectomized mice. PM crude extract (PME) significantly down-regulated the expression of RANKL mRNA with no change in the OPG level whereas MR elevated the expression of OPG mRNA with lowering level of RANKL mRNA, resulting in the increased OPG/RANKL ratio, and consequently lead to lowering progression of osteoporosis at molecular level. These findings revealed potential of PME and MR on bone loss prevention via increasing the ratio of OPG to RANKL (osteoformation/osteoresorption) in liver of ovariectomized mice. Therefore, using PME and MR as alternative hormone replacement therapy of E2 might be beneficial recommended due to advantageous on regulation of osteoporosis related genes.     

OPG/RANKL/RANK系统的研究进展

OPG/RANKL/RANK系统是近年来骨科研究领域中的重大突破,研究发现许多激素、细胞因子等均通过直接或间接的调节骨保护素(osteoprotegerin,OPG),核因子-κB受体活化因子配体(receptor activator ofNF-κB ligand,RANKL)的表达,调控OPG、RANKL和核因子-κB受体活化因子(recep-tor activator of NF-κB,RANK)之间的比例,从而介导破骨细胞的分化和功能而达到抗骨质疏松或致骨质疏松的作用。现就OPG/RANKL/RANK系统在骨质疏松中的作用做一综述。     

Effects of dietary calcium to available phosphorus ratios on bone metabolism and osteoclast activity of the OPG /RANK/RANKL signalling pathway in piglets

Hydroxyapatite, a mineral form of calcium (Ca) and phosphorus (P) that gives bones their rigidity, is the major and essential component of bones and teeth in the human and animal body. A suitable ratio of Ca and P is vital for bone growth. The aim of this study was to explore the effects of dietary calcium to available phosphorus ratios (Ca/AP) on bone metabolism and osteoclast activity of the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) signalling pathway in piglets. At days 15 and 29, the piglets were assessed for growth performance, blood indicators, cytokines and the OPG/RANK/RANKL signalling pathway. Our results showed that piglets fed a dietary Ca/AP ratio of 2:1 increases growth performance and regulates blood indicators and cytokines (parathyroid hormone (PTH), calcitonin (CT), vitamin D₃ (VD₃)_, insulin‐like growth factor‐1 (IGF‐1), transforming growth factor‐β (TGF‐β), interleukin‐1 (IL‐1), interleukin‐6 (IL‐6), carboxyterminal propeptide of type I procollagen (PICP), tartrate‐resistant acid phosphatase (TRACP), alkaline phosphatase (ALP) and osteocalcin (OCN) content). We also demonstrated that this ratio affects hormone secretion and further bone metabolism through the OPG/RANK/RANKL signalling pathway of osteoclasts. These results indicate that a suitable dietary Ca/AP ratio is vital for bone growth and reduce the incidence of bone diseases such as osteoporosis, providing a practical basis for the raising of piglets.