转化生长因子β与骨质疏松症关系的研究进展

转化生长因子β是骨代谢调节中重要的相关因子,它能刺激成骨细胞增殖、分化,促进细胞外基质的合成,减少骨转换,促进骨与软骨的形成,加速破骨细胞凋亡。因此在骨质疏松症的发病过程中起着重要作用,备受人们重视。本文就其与骨质疏松症相关性进行综述。     

骨质疏松症的诊治及应用间充质干细胞的治疗现状

骨质疏松症是一种系统性的代谢性骨骼疾病,其特征是骨量减少和骨微结构退化,导致骨骼脆性和骨折风险的增加。在成人中,骨髓间充质干细胞在骨骼中主要分化为成骨细胞和脂肪细胞,当其分化失衡,分化的脂肪细胞增多,成骨细胞减少,最终会演变成骨质疏松症。骨质疏松症越来越被认为是一个主要的公共健康问题,对全世界超过2亿人有影响,每年造成...     

新型骨质疏松症治疗药abaloparatide的作用机制与临床评价

Abaloparatide是Radius Health公司开发的一种治疗骨质疏松症的甲状旁腺激素类似物,其能诱导成骨细胞增殖和分化,促进骨形成,增加骨量,改善骨质疏松症状。2017年4月28日获FDA批准上市用于绝经后骨质疏松症的治疗。本文对其作用机制、药动学、临床评价、安全性等进行综述,旨在为临床用药提供参考。     

骨质疏松症的诊治及应用间充质干细胞的治疗现状

骨质疏松症是一种系统性的代谢性骨骼疾病, 其特征是骨量减少和骨微结构退化, 导致骨骼脆性和骨折风险的增加。在成人中, 骨髓间充质干细胞在骨骼中主要分化为成骨细胞和脂肪细胞, 当其分化失衡, 分化的脂肪细胞增多, 成骨细胞减少, 最终会演变成骨质疏松症。骨质疏松症越来越被认为是一个主要的公共健康问题, 对全世界超过2亿人有影响, 每年造成超过890万的骨折, 其中以髋骨骨折为主。随着人口老龄化的加剧, 花费在骨质疏松症的个人和社会成本逐年增加, 这对公共卫生保健体系提出了挑战。因此, 早期预防和诊断骨质疏松症的重要性不言而喻。此外, 由于间充质干细胞有成骨潜能, 且被发现可用于骨骼的修复和维护, 自体、异体或转基因骨髓间充质干细胞移植可有效增加骨量和骨密度, 增加骨机械强度, 纠正骨代谢失衡, 其有望成为骨质疏松症治疗的新策略和方法。本文将围绕骨质疏松症的诊断、治疗和间充质干细胞的应用现状展开如下综述。     

基于Wnt/β联蛋白信号通路探讨中医药防治骨质疏松症的研究进展

<正>骨质疏松症是一种与年龄增长相关的全身代谢性骨病。随着世界人口老龄化进程的发展,骨质疏松症已成为全球性日益重要的公共卫生问题[1]。在骨质疏松症的预防和治疗过程中,Wnt/β-联蛋白(catenin)信号通路通过促进成骨细胞的分化,在促进骨形成等方面发挥重要作用。实验研究发现,Wnt/β-catenin信号传导途径发挥促进成骨细胞分     

黄酮类化合物对成骨细胞作用机制的研究进展

骨质疏松症的病理学基础是成骨能力的降低和骨吸收的加快,促进成骨细胞的成骨能力是治疗骨质疏松症的重要方法之一。淫羊藿苷、柚皮苷、大豆苷元等黄酮类化合物可以通过多种信号转导途径影响成骨细胞增殖、分化及矿化功能,其中包括雌激素受体途径、骨形态发生蛋白2途径、丝/苏氨酸蛋白激酶途径、Wnt/β-连蛋白途径等。     

中药治疗骨质疏松症的研究进展

骨质疏松症是一种以骨量减少,骨的微观结构退化为特征,导致骨脆性增加的一种全身性代谢性骨骼疾病,以骨痛及腰背痛、驼背、易发骨折为三大主要症状。临床上分为三型：原发性、继发性以及特发性,以原发性最为多见。随着人口老龄化的日趋明显,骨质疏松症的患病率日益升高。目前,西药治疗骨质疏松症的方法主要有：①抗吸收疗法,主要是对抗骨动态平衡中的再吸收作用,主要用药有雌激素、二磷酸盐、选择性雌激素受体拮抗药、降钙素等。②合成代谢疗法,主要是促进骨形成。常用药物有甲状旁腺素、氟化物、雄性激素和蛋白同化剂等。③促进骨矿化法,药物主要有钙和维生素D。然而,西药治疗在不同程度上存在着远期疗效不理想,副作用大,药品价格昂贵等缺点。近年来,中药治疗骨质疏松症受到重视,并取得一定进展,现综述如下。     

骨质疏松症药物治疗研究进展

随着老龄化社会的来临,骨质疏松症的发病率逐渐升高,成为影响绝经后妇女和中、老年人健康的严重公共卫生问题,造成巨大的经济和社会负担。治疗骨质疏松症的药物的作用机制主要包括两个方面,即抑制骨吸收和促进骨形成。本文综述骨质疏松症药物治疗的研究进展。     

骨质疏松症药物治疗研究进展

随着老龄化社会的来临,骨质疏松症的发病率逐渐升高,成为影响绝经后妇女和中、老年人健康的严重公共卫生问题,造成巨大的经济和社会负担。治疗骨质疏松症的药物的作用机制主要包括两个方面,即抑制骨吸收和促进骨形成。本文综述骨质疏松症药物治疗的研究进展。     

骨形态发生蛋白与抗骨质疏松药物研究进展

骨形态发生蛋白能够增加成骨细胞分化的标志酶——碱性磷酸酶和骨钙蛋白等基因的表达，促进新骨形成及骨的层次化，在成骨细胞分化过程中起关键作用，有可能成为骨质疏松症防治药物的重要作用靶点。随着对骨形态发生蛋白2（BMP-2）研究的深入，越来越多的化合物破发现有上调BMP-2的作用，其中包括他汀类药物、白藜芦醇、秦皮素、红曲及雌激素等。现就近年来在骨形成的分子机制和以骨形态形成蛋白为靶点抗骨质疏松药物的研究进展进行综述。     

Puerarin stimulates osteoblasts differentiation and bone formation through estrogen receptor,p38 MAPK,and Wnt/β-catenin pathways

Puerarin is an isoflavone extracted from Radix Puerariae, a traditional Chinese herb used to treat many diseases such as osteoporosis. In this study, puerarin was shown to stimulate alkaline phosphatase (ALP) activity, type I collagen (Col I) secretion, and mineralized nodules formation of primary osteoblasts. Whereas the estrogen receptor (ER) antagonist ICI 182780 was able to reduce the increase in ALP activity and Col I secretion induced by puerarin. Furthermore, puerarin was shown to elevate levels of phospho-p38 mitogen-activated protein kinase (MAPK) and β-catenin proteins in a time-dependent manner. Pretreatment of osteoblasts with ICI 182780 can reduce this elevation, whereas pretreatment with p38 MAPK inhibitor SB 203580 did not affect the increase of β-catenin protein. Meanwhile, intragastric administration of puerarin protected against reduction in bone mineral density and bone mineral content in ovariectomized rats, and improved femur trabecular bone structure. Taken together, ER, p38 MAPK, and Wnt/β-catenin pathways were involved in puerarin-stimulated osteoblasts differentiation and bone formation.     

Stimulatory effect of puerarin on bone formation through activation of PI3K/Akt pathway in rat calvaria osteoblasts

Puerarin, a natural isoflavonoid found in Chinese Pueraria lobata (Wild.) Ohwi, has received increasing attention because of its possible role in the prevention of osteoporosis. However, the relationship between puerarin and bone formation remains unknown. In the present study, rat osteoblasts isolated from newborn Wistar rats were used to investigate the effect of puerarin on osteoblasts, and its possible molecular mechanism. Data showed that puerarin caused a significant increase in cell viability, alkaline phosphatase (ALP) activity and mineral nodules formation in osteoblasts, suggesting that puerarin had a stimulatory effect on osteoblastic bone formation. This functional improvement by puerarin was accompanied by activation and nuclear translocation of Akt. Furthermore, puerarin-stimulated osteoblastic growth, Akt activation and redistribution were significantly blocked by the specific PI3K inhibitor, LY294002. These results strongly suggested that puerarin stimulated osteoblastic proliferation and Akt activation in a PI3K-dependent manner. In summary, puerarin derived from Chinese Pueraria lobata (Wild.) Ohwi can promote bone formation in cultured rat osteoblasts, which might be mediated by activation of the PI3K/Akt pathway. DMEM:Dulbecco's modification of Eagel's medium PBS:phosphate buffered saline DMSO:dimethyl sulfoxide EDTA:ethylene diamine tetraacetic acid SDS:sodium dodecyl sulfate SDS-PAGE:sodium dodecylsulfate polyacrylamide gel electrophoresis FITC:fluorescein isothiocyanate HRP:horseradish peroxidase PI3K:phosphatidylinositol 3-kinase.     

辛伐他汀对体外成骨细胞、破骨细胞的影响

目的 探讨辛伐他汀对体外培养成骨细胞、破骨细胞的影响.方法 分离SD大鼠成骨细胞、破骨细胞,体外培养时给予辛伐他汀刺激,观察药物对成骨细胞增殖率和碱性磷酸酶以及骨细胞骨吸收的影响.结果 辛伐他汀10~(-6)～10~(-9)mol/L对碱性磷酸酶的分泌有明显促进作用,10~(-6)～10~(-8)mol/L的辛伐他汀既促进成骨细胞的增殖,又抑制破骨细胞的骨吸收.结论 辛伐他汀在体外促进骨形成、抑制骨吸收,有望成为治疗骨质疏松的约物.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

过氧化物酶体增殖物激活受体γ及其激动剂噻唑烷二酮类药物对骨骼成骨的影响及作用机制

过氧化物酶体增殖物激活受体γ(PPARγ)及配体是影响骨髓间充质干细胞分化与成熟的重要调控因子,可通过降低骨钙素、骨形成蛋白2等成骨细胞特异性成熟因子的表达,抑制成骨细胞的分化,亦可诱导成骨细胞的凋亡,最终导致骨丢失。目前普遍认为PPARγ参与了老年性骨质疏松、绝经后骨质疏松和继发性骨质疏松的发生、发展。PPARγ激动剂噻唑烷二酮类药物(TZDs)因其导致骨量降低、增加骨折发生率而备受争议,通过化学结构修饰将有可能避免这一不良反应发生。     

葛根素通过NO信号通路促进体外培养大鼠骨髓间充质细胞成骨性分化

目的 观察葛根素促进体外培养大鼠骨髓间充质细胞成骨性分化过程中是否激活NO信号通路。方法 一氧化氮合成酶阻断剂（nitric oxide synthase inhibitors,LNMA）预处理大鼠骨髓间充质细胞12 h后,使用葛根素处理骨髓间充质细胞不同时间,观察其对骨钙素（osteocalcin,OC）含量,碱性磷酸酶（alkaline phosphatase,ALP）活性和钙化结节染色,Runx-2、OSX、BMP-2和Collagen-1 mRNA表达水平的影响,以及NO和3''-5''-环鸟苷一磷酸（cGMP）含量的影响。结果 葛根素对骨髓间充质细胞增殖活性存在浓度的依赖性,其中1×10^-6 mol·L^-1促进其增殖活性最高,并显著提高了该细胞中ALP活性。预先使用LNMA处理大鼠骨髓间充质细胞后,葛根素提高该细胞中ALP活性、OC含量、钙化能力和Runx-2、OSX、BMP-2和Collagen-1 mRNA的表达水平作用均受到抑制,以及葛根素提高NO和cGMP含量能力受到抑制。结论 葛根素能有效促进体外培养大鼠骨髓间充质细胞成熟与矿化,并需要NO信号通路的参与。     

Myricetin Loaded Nano-micelles Delivery System Reduces Bone Loss Induced by Ovariectomy in Rats Through Inhibition of Osteoclast Formation

In recent years, much attention has been paid to the therapeutic effects of phytochemicals on osteoporosis. Other studies have shown that myricetin (MY) could promote osteogenic activity and inhibit osteoclastic effect, albeit little is known about effect of MY micellar system on osteoporosis. Therefore, we sought to discuss the therapeutic effect and mechanism of MY-loaded bone-targeting micelles on osteoporosis induced by ovariectomy (OVA) in rats. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles were prepared via ethanol injection method, while in vitro release study, bone targeting, pharmacokinetic studies, and the effect on proliferation of osteoblasts were investigated. Further, the therapeutic effect on osteoporosis was studied through ovariectomized rats. Compared with free MY, oral bioavailability of AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles in rats was increased by 3.54 times. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles exhibited bone targeting potential, and could significantly increase the activity of alkaline phosphatase and promote the proliferation of osteoblasts. Importantly, AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles mainly regulated bone metabolism by inhibiting bone resorption, thereby improving the symptoms of osteoporosis in OVA rats. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles substantially enhanced the oral bioavailability of MY and demonstrated good bone targeting capability, thereby suggesting its prospect as carrier for osteoporotic improvement in OVA rats.     

Osteoblasts and osteoclasts in bone remodeling and inflammation

Bone homeostasis is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Osteoblasts not only play a central role in bone formation by synthesizing multiple bone matrix proteins, but regulate osteoclast maturation by soluble factors and cognate interaction, resulting in bone resorption. Osteoclast maturation requires stimulation by RANKL expressed on osteoblasts, and the cognate interaction is mediated by firm adhesion via ICAM-1. During the processes, pro-inflammatory cytokines such as IL-1 and TNF-alpha, cause an imbalance in bone metabolism, by favoring bone resorption via the induction of RANKL and ICAM-1 on osteoblasts. These inflammatory signals originate from the immune system, the largest source of cell-derived regulatory signals, and such immunological signals to the bone are transmitted primarily via osteoblasts to induce osteoclast maturation, resulting in secondary osteoporosis. Actually, such phenomena mainly occur at the interface between proliferating synovium and bone tissue in rheumatoid arthritis (RA). Thus, therapeutic strategies for these conditions, an anti-TNF-alpha antibody and an IL-1 receptor antagonist, effective for treating RA disease activity, also reduce secondary osteoporosis and joint destruction. Based on an improved understanding of immune signals, investigation of the suppression of cell functions may lead to improved understanding and better treatment of diseases of bone metabolism and osteoporosis.     

右归饮对去势雌性小鼠骨质疏松的治疗作用

目的探讨右归饮对去势雌性小鼠骨质疏松的影响,并对其作用机制进行研究。方法将C57BL/6雌性小鼠去卵巢手术模拟骨质疏松症,饲养12周后,分别分为假手术组、模型组、雷洛昔芬组、右归饮组,每组各9只,模型组、假手术组ig生理盐水,右归饮组ig右归饮溶液。雷洛昔芬组ig盐酸雷洛昔芬溶液10 mg/kg。每天每只均给药0.2 m L,连续给药5周,眼球取血,测定血清中生化指标和钙、磷水平;将动物处死,测定骨形态计量指标和做Micro-CT。分离并培养骨内间充质干细胞,测定细胞的增殖和分化。结果与模型组比较,右归饮组的骨密度、骨体积分数、骨小梁平均厚度、骨小梁数量均显著升高,骨表面积/骨体积和骨小梁分离度均显著降低,差异具有统计学意义(P0.05)。右归饮组I型胶原氨基端前肽(P1NP)水平较模型组显著升高(P0.05),胶原羧基端(CTx)水平比模型组略高一点,差异均无统计学意义。右归饮组钙、磷水平与模型组各指标之间的差异均无统计学意义。与模型组比较,右归饮组细胞呈增长趋势,但增长率较其他组相对较低(P0.01),倍数变化显著升高(P0.01)。结论右归饮对去势雌性小鼠骨质疏松有治疗作用,可能是通过促进间充质干细胞分化成成骨细胞,从而刺激骨形成,达到有效抑制小鼠骨的丢失。