Protective effects of resveratrol on postmenopausal osteoporosis： regulation of SIRT1-NF-κB signaling pathway

Postmenopausal osteoporosis severely jeopardizes human health. Seeking for therapeutic drugs without side effects is of great necessity. Our study was designed to investigate whether resveratrol, an agonist of SIRT1, could have favor- able effect on osteoporosis and to explore the underlying mechanisms. Rat osteoporosis model （ovariectomy group, OVX） was established by bilateral ovariectomy. Three dif- ferent doses of resveratrol were used： 5 mg/kg/d （low- dosed, RESCD）, 25 mg/kg/d （medium-dosed, RESMD）, and 45 mg/kg/d （high-dosed, RESUD）. Results showed that RESLD did not show any significant effect on OVX altera- tions, while RESMD and RESXD significantly elevated the decreased bone mineral density induced by osteoporosis （RESMD 0.205±0.023, RESm） 0.214 ± 0.053 vs. OVX 0.165 ± 0.050 g/cm2 respectively; P 〈 0.05）. Serum markers alkaline phosphatase （ALP） and osteocalcin were moderately restored by resveratrol. Moreover, resveratrol improved bone structure in OVX rats, demonstrated by hematoxylin-eosin staining and micro-computed tomo- graphic results. In vitro results revealed that resveratrol promoted osteoblast differentiation of bone marrow mesen- chymal stromal cells, evidenced by the increase of ALP generation and mRNA expression of collagen 1 （P 〈 0.05; RESMD, RESm） vs. control group）. SIRT1 gene silencing by siRNA transfection blocked these beneficial effects of resveratrol （P〈0.05; RES ＋ SIRT1^KD vs RES^HD）. Western blot results showed that resveratrol activated SIRT1 and subsequently suppressed the activity of NF-κB with decreased expression level of p-IκBa and NF-κB p65 （P〈 0.05）. Our findings verified the effects of specific dosed resveratrol on postmenopausal osteoporosis through osteoblast differentiation via SIRT1-NF-κB signaling pathway. This study suggested the therapeutic potential of resveratroi against osteoporosis and stressed the importance of effective doses.     

老年女性类风湿关节炎合并骨质疏松症的代谢特点分析

目的:探讨老年女性类风湿关节炎(RA)合并骨质疏松症的代谢特点。方法:选择老年绝经后女性RA患者共59例,检测患者血生化代谢指标如血糖、血脂、CRP等和骨代谢指标如骨钙素(OC)、β-胶原特殊序列(β-Crosslaps)甲状旁腺素(iPTH)等,并进行统计分析。结果:骨质疏松患者的绝经时间、病程长度、OC、β-Crosslaps、iPTH显著高于骨量正常和骨量减少的患者,25羟基维生素D显著低于骨量正常和骨量减少的患者(P均0.05)。RA患者的骨密度水平与是否使用激素和X线分期情况无关。结论:老年女性RA患者易发生骨质疏松,出现骨质疏松的RA女性患者绝经时间更长,可出现脂代谢紊乱及明显的维生素D缺乏,并具有高转换型骨代谢特点。     

SCT-OGP的融合表达与活性的初步研究

根据天然鲑鱼降钙素(Salmoncalcitonin,SCT)和骨生长肽(OsteogenicGrowthPeptide,OGP)的序列,人工合成了6个DNA片段,进行退火、连接和转化后,获得含有SCT与OGP融合基因的pPIC9-SCT-OGP表达载体,经测序后将此重组质粒电击转化毕赤酵母GS115,通过培养、筛选以及SDS-PAGE鉴定,在毕赤酵母中获得了SCT-OGP融合蛋白的可溶性表达,经分子筛纯化后在5kD左右可见单一条带。将此条带进行了N端氨基酸组分分析,证实此目的蛋白为SCT-OGP融合蛋白。MTT法显示SCT-OGP融合蛋白在体外可以促进成骨细胞和成纤维细胞增殖,以小鼠为模型的试验显示SCT-OGP融合蛋白在体内可以提高碱性磷酸酶活性和降低血钙,表明该融合蛋白具有抑制破骨细胞的活性和刺激成骨细胞增殖的活性,从而提示该融合蛋白具有治疗骨质疏松症的药用潜力。     

生活习惯对骨质疏松症的影响

按照WHO定义,骨质疏松症是一种以骨量低下、骨微结构破坏,导致骨脆性增加,易发生骨折为特征的全身性骨病。虽然大多数患者并不直接引起死亡,但对其健康、生活质量、社会负担带来的影响非常重大。骨质疏松症已经成为一个世界范围的、主要的、越来越严重的公共问题。骨质疏松症的发生受多种因素影响,主要包括环境和遗传两方面。已经确定峰值骨密度的60％～80％由遗传决定,20％由环境决定。环境因素的影响虽小,但是可控制,而作为环境的重要组成部分,生活习惯的控制无疑对骨质疏松症的预防起积极作用。     

PTH融合蛋白研究进展

甲状旁腺激素(Parathyroid Hormone)是由甲状旁腺主细胞合成和分泌的一种单链多肽激素,是人体内维持血钙恒定的主要激素.PTH在人体内的生理功能非常广泛,PTH类似物已被开发成为治疗骨质疏松症的一系列新型药物.为了克服人PTH分子量小、在人体内代谢快、临床应用不方便的缺点,长效融合蛋白体的研究逐渐成为一种趋势,并且取得了一定的成就.主要依据国内外对PTH重组体和PTH融合蛋白体的研究现状,对PTH的构效关系与生理活性、PTH类似物的研究成果及PTH的应用前景进行综述.     

大鼠骨组织内一些细胞因子和胶原蛋白基因的表达与雌激素和年龄 …

30 female SD rats (3 months old) are equally divided into three groups: ovariectomy (OVX) rats, sham-operated (SHO) rats and 17 beta estradiol (E2) treated OVX rats. For each group, mRNA was isolated from long bone at one month and three months after surgery, respectively. mRNA was reverse transcribed into single strand cDNA and then used as a probe hybridizing to the DNA fragments of col I alpha(1), col I alpha(2), col III, col V, fibronectin, IL-1, IL-6, TGF-beta, LIF, TNF-alpha, TNF-beta by reverse northern and dot blot hybrization. The housekeeping gene, gapdh, was used as an internal control. The results show that in bone of rat, the stable expression of col I alpha (1), col I alpha(2) and col III are related to age not ovariectomy, while supplement with E2 can inhibit the expression of col III and col I alpha(2) completely. The expression of col V, IL-1, IL-6 can be inhibited by estrogen and recovered by removal of estrogen by OVX, then addition of E2 decreased it to the normal level. The expression of TGF-beta is also inhibited by estrogen. It increased during one month after overiectomy, and partially decreased in E2 complemented rat. Three months after surgery, the level of increasing and decreasing is less evident as two months ago. It seems that in young SD rat, the expression of TGF-beta is related to both estrogen and age.     

肌肉骨骼减少症发病机制及其运动防治效果

肌肉骨骼减少症（osteosarcopenia,OS）是一种多因素、多病因的退行性代谢综合征,其影响因素可能与衰老导致的机械、遗传、炎症因子、内分泌紊乱以及生活方式不规律相关。OS患者具有更高跌倒、骨折、活动障碍和死亡的风险,随着中国全球老龄化进程的加快,OS已经成为不容忽视的公共健康问题。近年来,国内外学者针对OS开展了大量的研究,但其发病机制仍不清楚。了解与OS相关的信号通路对进一步研究其发病机制和寻找治疗的新靶点具有重要意义。而运动作为现有效果强、持续性好的非药物治疗方式,能够增加老年人肌肉质量、提高骨密度、改善生活质量等,从而有效地预防和改善OS。本文主要就OS的流行病学、诊断标准、共同参与调节肌细胞与骨骼细胞代谢过程的相关信号通路（PI3K/Akt通路、Wnt/β-catenin通路、Notch通路、NF-κB通路）,以及不同运动方式对OS的干预效果等方面进行综述,以期为临床治疗OS提供理论依据,提高老年疾病的预防能力。     

肠道微生态与骨质疏松症

骨质疏松症是一种骨代谢障碍所致的全身性骨骼疾病,严重威胁着老龄人群的身心健康。肠道微生态(intestinal microecology, GM)是人体内最重要且最为复杂的微生态系统,对营养吸收、免疫调节、免疫防御、生长发育等有重要作用。GM失衡与炎症性肠病、糖尿病、心血管疾病、帕金森病、骨质疏松症等疾病的发生发展密切相关。肠道菌群丰度及菌群结构的改变可能与骨量减少有关,且经益生菌、益生元及天然中草药改善GM失衡后,骨质疏松症得到改善。本文就GM与骨质疏松症之间的关系、可能机制及治疗进展进行综述。     

预测骨质疏松症新技术

日本大阪齿科大学开发出一种根据颌骨的骨密度来诊断或预测全身骨骼是否出现骨质疏松症的技术。 骨质疏松症患者的颌骨骨密度降低比腰椎降低得更早。通过对34名50岁至69岁的女性为对象,拍摄了其下颌的前臼齿和牙槽骨的X光片,然后,利用计算机的专用软件,计算出骨密度,