淫羊藿苷药理作用的研究进展

淫羊藿为中国传统药用植物,淫羊藿苷是淫羊藿中的主要活性成分.现代药理学研究表明淫羊藿苷具有改善心脑血管功能、加强性腺功能、增强机体免疫功能、抑制破骨细胞,促进成骨细胞生长、延缓衰老、抗肿瘤、抗病毒等生理活性.本文就近年来有关淫羊藿苷药理作用的研究进行综述.     

miR-214对骨形成的抑制作用

越来越多的研究表明microRNA广泛参与骨代谢的调控,调节骨髓间充质干细胞、成骨及破骨细胞的增殖及分化,调控骨形成与骨吸收之间的平衡,在维持骨代谢平衡中发挥重要作用。近年来有研究报道老年性骨质疏松、绝经后骨质疏松均与miR-214的高表达有关。miR-214通过靶向作用于Osterix、ATF-4、FGFR1、Pten以及LZTS1等基因调控骨髓间充质干细胞、成骨细胞以及破骨细胞等骨组织细胞的增殖及分化,进而抑制骨形成,促进骨吸收。本文主要综述了miR-214对骨髓间充质干细胞、成骨细胞以及破骨细胞分化的调控作用,旨在探讨miR-214对骨形成的抑制作用,为骨质疏松等骨疾病的诊断及治疗提供理论依据。     

淫羊藿属植物化学成分及药理活性研究进展

淫羊藿属植物是中国传统的药用植物,淫羊藿总黄酮是淫羊藿属植物中的主要活性成分,迄今从国内淫羊藿属13种植物中分离鉴定的黄酮类化合物有106种.药理研究表明,淫羊藿总黄酮具有抑制破骨细胞、促进成骨细胞生长、抗抑郁、增强免疫调节、保护心脑血管系统、抑菌、抗炎、抗病毒、抗氧化、抗衰老、抗肿瘤等多方面的药理活性.本文对国内外有关淫羊藿属植物的化学成分及药理作用的研究进展进行综述,为进一步研究与开发利用提供参考.     

淫羊藿苷促进体外培养骨髓间充质细胞成骨性分化活性强于蛇床子素

比较研究蛇床子素与淫羊藿苷处理对体外培养的大鼠骨髓间充质细胞(rat bone marrow stromal cell, rBMSC)成骨性分化的影响.从体外分离培养的大鼠骨髓间充质细胞,筛选出最佳的蛇床子素和淫羊藿苷处理的浓度为1×10-5 mol/L, 然后用最佳的浓度对体外培养的大鼠骨髓间充质细胞进行药物干预;在药物干预后的第3、6、9、12和15 d后测定碱性磷酸酶活性（alkaline phosphatase,ALP）和钙含量;第12 d 进行钙化结节茜素红染色;第12 h、24 h、48 h、72 h和96 h 对OXS、Runx-2、骨形态发生蛋白(bone morphogenetic protein,BMP-2)和collagen-I mRNA 表达水平进行real-time RT-PCR检测.结果显示,浓度为1×10-5 mol/L蛇床子素和淫羊藿苷干预均可提高体外培养的骨髓间充质细胞ALP活性,增加Ca含量,提高Runx、OXS、BMP-2和collagen-1 mRNA的表达水平.同时,淫羊藿苷在促进体外培养骨髓间充质细胞成骨性分化活性强于蛇床子素.     

调控软骨形成的信号通路及相关因子在骨髓间充质干细胞骨向分化中的作用*

骨髓间充质干细胞是一类具有自我复制和多向分化潜能的成体干细胞,可以通过定向诱导分化为成骨细胞、软骨细胞、脂肪细胞等,是目前骨再生医学和细胞治疗研究最多的理想种子细胞。在骨缺损的修复过程中,骨髓间充质干细胞内成软骨相关基因表达升高进而分化为软骨细胞,后期随着成骨细胞和破骨细胞的形成及血管长入,软骨基质逐步降解并被骨基质所替换。软骨细胞参与了骨缺损前期的修复过程,调控软骨形成的信号通路及相关因子不仅调控骨髓间充质干细胞成软骨细胞分化,同时在成骨细胞分化过程中也发挥着重要的作用。对调控软骨形成的信号通路及相关因子在骨髓间充质干细胞骨向分化中的调控作用和研究现状进行了总结,以期为临床寻找更好的治疗骨缺损的方法提供理论依据和研究方向。     

黄芩总黄酮及黄芩苷对大鼠成骨细胞及破骨细胞活性的研究

为观察黄芩总黄酮及黄芩苷对新生大鼠成骨细胞及破骨细胞活性影响,给SD大鼠灌胃给药3 d后取含药血清,分离成骨细胞及破骨细胞体外培养,MTT法检测成骨细胞活性,AKP检测成骨细胞分化程度,用骨吸收陷窝数量评价破骨细胞活性。结果表明,与对照组相比,含黄芩总黄酮及黄芩苷血清剂量依赖性地促进成骨细胞增殖;其通过促进成骨细胞的增殖和分化,抑制破骨细胞的活性,对临床骨质疏松的防治具有积极意义。     

淫羊藿苷对大鼠正畸牙齿压力区牙周组织RANKL和Wnt3a表达的影响

目的:观察不同剂量的淫羊藿苷对大鼠正畸牙齿移动时压力区牙周组织中RANKL和Wnt3a表达的影响。方法:将24只健康雄性SD大鼠随机分为4组,根据淫羊藿苷灌胃的剂量分为生理盐水组(对照组)、1 mg/kg淫羊藿苷组、3 mg/kg淫羊藿苷组、5mg/kg淫羊藿苷组(实验组),使用50 g力近中移动左侧上颌第一磨牙。通过免疫组化方法检测压力区牙周组织中RANKL和Wnt3a蛋白的表达。结果:生理盐水组上颌第一磨牙压力区牙根和牙槽骨表面粗糙,牙周膜间隙变窄,可见骨吸收陷窝和破骨细胞,不同剂量淫羊藿苷组牙周膜间隙趋于恢复正常,骨吸收陷窝出现明显减少。RANKL和Wnt3a在生理盐水组和淫羊藿苷组的压力区牙周组织中都有表达。与生理盐水组比较,不同剂量淫羊藿苷组压力区牙周组织中RANKL的表达均显著降低,Wnt3a的表达均明显增加,且RANKL的表达随淫羊藿苷剂量的增加而逐渐减少(P0.05),Wnt3a的表达随淫羊藿苷剂量的增加明显增加(P0.05)。结论:不同剂量淫羊藿苷能减少正畸时牙齿移动过程中压力区牙周组织中RANKL的表达,增加Wnt3a的表达,且作用与其剂量具有一定的相关性。     

光照对淫羊藿活性成分生物合成的影响

淫羊藿作为传统的中药材,具有补肾阳、强筋骨、祛风湿等功效.其主要功能活性成分为黄酮醇苷成分淫羊藿苷、朝藿定A、B、C等.本实验在武汉植物园内的药园和园外园两个不同生长环境下,研究两种不同光照对巫山淫羊藿(Epimedium wushanense T.S.Ying)WY品系和箭叶淫羊藿(Epimedium sagittatum( Sieb.& Zucc.)Maxim.) LT1、HN3品系4种主要活性成分生物合成的影响.结果显示,在药园环境生长的淫羊藿的光合速率要高于园外园生长的淫羊藿,药园生长的箭叶淫羊藿LT1、HN3品系的4种活性成分含量均高于园外园生长的同品系,而巫山淫羊藿WY品系则相反.光合速率对4种活性成分含量的积累有一定影响,与朝藿定A、B和淫羊藿苷含量呈显著正相关,与朝藿定C含量呈显著负相关.文中对光合速率与活性成分积累间的关系进行了讨论,还针对不同的淫羊藿品系提出了相应的栽培建议.     

淫羊藿提取物的抗炎作用及其机制

淫羊藿是一种常用的传统中药。黄酮类成分是淫羊藿的主要有效成分,其中淫羊藿苷是含量最高的单体成分,淫羊藿素是淫羊藿苷的代谢产物。最近十余年来,学者对淫羊藿提取物的药理作用进行了许多研究,表明淫羊藿黄酮,尤其是淫羊藿苷及其衍生物,在骨质疏松症、骨关节炎、神经和精神疾病、动脉粥样硬化、哮喘和肺部疾病、炎症性肠病、肾脏疾病、皮肤病、自身免疫性疾病和癌症等多个与慢性炎症有关的疾病模型中显示了良好的抗炎作用。淫羊藿苷及其衍生物发挥抗炎作用的分子机制主要包括降低炎症细胞因子释放和NF-κB信号通路激活,抑制NLRP3/caspase-1/IL-1β、STAT和MAPK介导的信号传导通路,上调Nrf2/ARE/HO-1信号通路以及糖皮质激素受体和雌激素受体下游信号通路等。本文综述了该领域的近期研究进展,提示淫羊藿及其所含的活性化合物具有治疗多种慢性炎症相关疾病的潜力。     

淫羊藿提取物的抗炎作用及其机制（英文）

淫羊藿是一种常用的传统中药.黄酮类成分是淫羊藿的主要有效成分,其中淫羊藿苷是含量最高的单体成分,淫羊藿素是淫羊藿苷的代谢产物.最近10余年来,学者对淫羊藿提取物的药理作用进行了许多研究,表明淫羊藿黄酮,尤其是淫羊藿苷及其衍生物,在骨质疏松症、骨关节炎、神经和精神疾病、动脉粥样硬化、哮喘和肺部疾病、炎症性肠病、肾脏疾病、皮肤病、自身免疫性疾病和癌症等多个与慢性炎症有关的疾病模型中显示了良好的抗炎作用.淫羊藿苷及其衍生物发挥抗炎作用的分子机制主要包括降低炎症细胞因子释放和NF-κB信号通路激活,抑制NLRP3/caspase-1/IL-1β、STAT和MAPK介导的信号传导通路,上调Nrf2/ARE/HO-1信号通路以及糖皮质激素受体和雌激素受体下游信号通路等.本文综述了该领域的近期研究进展,提示淫羊藿及其所含的活性化合物具有治疗多种慢性炎症相关疾病的潜力.     

Effects of electromagnetic fields on osteoporosis: A systematic literature review

ABSTRACT

Electromagnetic fields (EMFs) as a safe, effective and noninvasive treatment have been researched and used for many years in orthopedics, and the common use clinically is to promote fracture healing. The effects of EMFs on osteoporosis have not been well concerned. The balance between osteoblast and osteoclast activity as well as the balance between osteogenic differentiation and adipogenic differentiation of bone marrow mesenchymal stem cells plays an important role in the process of osteoporosis. A number of recent reports suggest that EMFs have a positive impact on the balances. In this review, we discuss the recent advances of EMFs in the treatment of osteoporosis from basic research to clinical study and introduce the possible mechanism. In addition, we presented future perspectives of application of EMFs for osteoporosis.     

Playing with bone and fat

The relationship between bone and fat formation within the bone marrow microenvironment is complex and remains an area of active investigation. Classical in vitro and in vivo studies strongly support an inverse relationship between the commitment of bone marrow-derived mesenchymal stem cells or stromal cells to the adipocyte and osteoblast lineage pathways. In this review, we focus on the recent literature exploring the mechanisms underlying these differentiation events and discuss their implications relevant to osteoporosis and regenerative medicine.     

Cannabinoid Receptor Type 1 Protects against Age- Related Osteoporosis by Regulating Osteoblast and Adipocyte Differentiation in Marrow Stromal Cells

Age-related osteoporosis is characterized by reduced bone formation and accumulation of fat in the bone marrow compartment. Here, we report that the type 1 cannabinoid receptor (CB1) regulates this process. Mice with CB1 deficiency (CB1^−/−) had increased peak bone mass due to reduced bone resorption, but developed age-related osteoporosis with reduced bone formation and accumulation of adipocytes in the bone marrow space. Marrow stromal cells from CB1^−/− mice had an enhanced capacity for adipocyte differentiation, a reduced capacity for osteoblast differentiation, and increased expression of phosphorylated CREB (pCREB) and PPARγ. Pharmacological blockade of CB1 receptors stimulated adipocyte differentiation, inhibited osteoblast differentiation, and increased cAMP and pCREB in osteoblast and adipocyte precursors. The CB1 receptor is therefore unique in that it regulates peak bone mass through an effect on osteoclast activity, but protects against age-related bone loss by regulating adipocyte and osteoblast differentiation of bone marrow stromal cells.     

Downregulated fat mass and obesity-associated protein inhibits bone resorption and osteoclastogenesis by nuclear factor-kappa B inactivation

During osteoporosis, fat mass and obesity-associated protein (FTO) promotes the shift of bone marrow mesenchymal stem cells to adipocytes and represses osteoblast activity. However, the role and mechanisms of FTO on osteoclast formation and bone resorption remain unknown. In this study, we investigated the effect of FTO on RAW264.7 cells and bone marrow monocytes (BMMs)-derived osteoclasts in vitro and observed the influence of FTO on ovariectomized (OVX) mice model to mimic postmenopausal osteoporosis in vivo. Results found that FTO was up-regulated in BMMs from OVX mice. Double immunofluorescence assay showed co-localization of FTO with tartrate-resistant acid phosphatase (TRAP) in femurs of OVX mice. FTO overexpression enhanced TRAP-positive osteoclasts and F-actin ring formation in RAW264.7 cells upon RANKL stimulation. The expression of osteoclast differentiation-related genes, including nuclear factor of activated T cells c1 (NFATc1) and c-FOS, was upregulated in BMMs and RAW264.7 cells after FTO overexpression. FTO overexpression induced the phosphorylation and nuclear translocation of factor-kappa B (NF-κB) p65 in BMMs and RAW264.7 cells exposed to RANKL. ChIP and dual-luciferase assays revealed that FTO overexpression contributed to RANKL-induced binding of NF-κB to NFATc1 promoter. Rescue experiments suggested that FTO overexpression-mediated osteoclast differentiation was suppressed after intervention with a NF-κB inhibitor pyrrolidine dithiocarbamate. Further in vivo evidence revealed that FTO knockdown increased bone trabecula and bone mineral density, inhibited bone resorption and osteoclastogenesis in osteoporotic mice. Collectively, our research demonstrates that downregulated FTO inhibits bone resorption and osteoclastogenesis through NF-κB inactivation, which provides a novel reference for osteoporosis treatment.     

影响骨髓间质干细胞向成骨细胞分化的调控因素

长期的骨骼废用引起的骨质减少主要归因于骨形成的减少,成骨细胞由具有多向分化潜能的间充质细胞经骨原细胞、前成骨细胞分化而来,骨髓间质干细胞是骨髓来源的具有多向分化潜能的干细胞,本文综述了骨髓间质干细胞向成骨细胞分化的调控因素,有助于增加对骨丢失的理解,并进行预防和治疗,为航天员和骨骼废用病人创造更健康的生活。     

Osteoblast physiology in normal and pathological conditions

Osteoblasts are mononucleated cells that are derived from mesenchymal stem cells and that are responsible for the synthesis and mineralization of bone during initial bone formation and later bone remodelling. Osteoblasts also have a role in the regulation of osteoclast activity through the receptor activator of nuclear factor κ-B ligand and osteoprotegerin. Abnormalities in osteoblast differentiation and activity occur in some common human diseases such as osteoporosis and osteoarthritis. Recent studies also suggest that osteoblast functions are compromised at sites of focal bone erosion in rheumatoid arthritis.     

A dual role of cholesterol in osteogenic differentiation of bone marrow stromal cells

Osteoblasts, the chief bone-forming cells, are differentiated from mesenchymal stromal/stem cells. Disruption of this differentiation process can cause osteoporosis, a bone disease characterized by low bone mass and deteriorated bone structure. Cholesterol has been implicated in pathogenesis of osteoporosis, and was recently identified as an endogenous activator of Hedgehog (Hh) signaling. However, its pathological and physiological roles in osteoblast differentiation are still poorly understood. Moreover, it is unclear whether these potential roles played by cholesterol are related to its capability to modulate Hh pathway. In this study, we investigated the role of exogenous versus endogenous cholesterol in osteogenesis and Hh pathway activation using ST2 cells, a bone marrow stromal cell line. We found that exogenous cholesterol significantly inhibited alkaline phosphatase (ALP) activity and messenger RNA expression of osteoblast markers genes (Alpl, Sp7, and Ibsp) while modestly activating expression of Gli1 (a readout of Hh signaling) under both basal osteogenic culture condition and Wnt3a treatment. Similarly, exogenous cholesterol suppressed osteogenic response of ST2 cells to sonic Hh (Shh) or purmorphamine (Purmo) treatment, which, however, was accompanied by diminished induction of Gli1, indicating the involvement of a Hh-dependent mechanism. Interestingly, depletion of endogenous cholesterol also reduced Shh-induced ALP activity and Gli1 expression. Likewise, cholesterol depletion inhibited osteogenic response to Purmo, although it did not affect Gli1 induction. Taken together, our findings have demonstrated that cholesterol plays a dual role in osteoblast differentiation likely through both Hh-dependent and -independent mechanisms.