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1Stem cell-based bone and dental regeneration: a view of microenvironmental modulation显示文摘In modern medicine,bone and dental loss and defects are common and widespread morbidities,for which regenerative therapy has shown great promise.Mesenchymal stem cells,obtained from various sources and playing an essential role in organ development and postnatal repair,have exhibited enormous potential for regenerating bone and dental tissue.Currently,mesenchymal stem cells (MSCs)-based bone and dental regeneration mainly includes two strategies: the rescue or mobilization of endogenous MSCs and the application of exogenous MSCs in cytotherapy or tissue engineering.Nevertheless,the efficacy of MSCbased regeneration is not always fulfilled,especially in diseased microenvironments.Specifically,the diseased microenvironment not only impairs the regenerative potential of resident MSCs but also controls the therapeutic efficacy of exogenous MSCs,both as donors and recipients.Accordingly,approaches targeting a diseased microenvironment have been established,including improving the diseased niche to restore endogenous MSCs,enhancing MSC resistance to a diseased microenvironment and renormalizing the microenvironment to guarantee MSC-mediated therapies.Moreover,the application of extracellular vesicles (EVs) as cell-free therapy has emerged as a promising therapeutic strategy.In this review,we summarize current knowledge regarding the tactics of MSC-based bone and dental regeneration and the decisive role of the microenvironment,emphasizing the therapeutic potential of microenvironment-targeting strategies in bone and dental regenerative medicine.Chenxi Zheng Ji Chen Shiyu Liu Yan Jin 2019International Journal of Oral Science2019,11,3:18
2Omentin-1 prevents inflammation-induced osteoporosis by downregulating the pro-inflammatory cytokines显示文摘Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout(omentin-1^(-/-)) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α(TNF-α), we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.Shan-Shan Rao Yin Hu Ping-Li Xie Jia Cao Zhen-Xing Wang Jiang-Hua Liu Hao Yin Jie Huang Yi-Juan Tan Juan Luo Ming-Jie Luo Si-Yuan Tang Tuan-Hui Chen Ling-Qing Yuan Er-Yuan Liao Ran Xu Zheng-Zhao Liu Chun-Yuan Chen Hui Xie 2018Bone Research2018,6,2:16
3Advancing application of mesenchymal stem cell-based bone tissue regeneration显示文摘Reconstruction of bone defects,especially the critical-sized defects,with mechanical integrity to the skeleton is important for a patient's rehabilitation,however,it still remains challenge.Utilizing biomaterials of human origin bone tissue for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural bone tissue with regard to its properties.However,not only efficacious and safe but also costeffective and convenient are important for regenerative biomaterials to achieve clinical translation and commercial success.Advances in our understanding of regenerative biomaterials and their roles in new bone formation potentially opened a new frontier in the fast-growing field of regenerative medicine.Taking inspiration from the role and multicomponent construction of native extracellular matrix(ECM)for cell accommodation,the ECM-mimicking biomaterials and the naturally decellularized ECM scaffolds were used to create new tissues for bone restoration.On the other hand,with the going deep in understanding of mesenchymal stem cells(MSCs),they have shown great promise to jumpstart and facilitate bone healing even in diseased microenvironments with pharmacology-based endogenous MSCs rescue/mobilization,systemic/local infusion of MSCs for cytotherapy,biomaterials-based approaches,cell-sheets/-aggregates technology and usage of subcellular vesicles of MSCs to achieve scaffolds-free or cell-free delivery system,all of them have been shown can improve MSCsmediated regeneration in preclinical studies and several clinical trials.Here,following an overview discussed autogenous/allogenic and ECM-based bone biomaterials for reconstructive surgery and applications of MSCsmediated bone healing and tissue engineering to further offer principles and effective strategies to optimize MSCs-based bone regeneration.Fengqing Shang Yang Yu Shiyu Liu Leiguo Ming Yongjie Zhang Zhifei Zhou Jiayu Zhao Yan Jin 2021Bioactive Materials2021,6,3:13
4驴奶和牛奶游离氨基酸成分分析研究显示文摘采用氨基酸分析仪对驴奶和牛奶中游离的氨基酸进行分析,比较其中的必需氨基酸和特殊生理功能氨基酸的相对含量。结果表明,驴奶的游离氨基酸中所含有的必需氨基酸、小儿/早产儿必需氨基酸及特殊生理活性氨基酸等均高于牛奶。可见在游离氨基酸相对含量方面,驴奶表现出显著优于牛奶的营养价值和保健功效。李宇 赵兵 蒋慧 张静 涂裔伟 姚路迅 贾薇 张奇 2017中国乳业2017,,10:6
5Histone demethylase LSD1 regulates bone mass by controlling WNT7B and BMP2 signaling in osteoblasts显示文摘Multiple regulatory mechanisms control osteoblast differentiation and function to ensure unperturbed skeletal formation and remodeling. In this study we identify histone lysine-specific demethylase 1(LSD1/KDM1 A) as a key epigenetic regulator of osteoblast differentiation. Knockdown of LSD1 promoted osteoblast differentiation of human mesenchymal stem cells(hMSCs)in vitro and mice lacking LSD1 in mesenchymal cells displayed increased bone mass secondary to accelerated osteoblast differentiation. Mechanistic in vitro studies revealed that LSD1 epigenetically regulates the expression of WNT7 B and BMP2. LSD1 deficiency resulted in increased BMP2 and WNT7 B expression in osteoblasts and enhanced bone formation, while downregulation of WNT7 B-and BMP2-related signaling using genetic mouse model or small-molecule inhibitors attenuated bone phenotype in vivo. Furthermore, the LSD1 inhibitor tranylcypromine(TCP) could increase bone mass in mice. These data identify LSD1 as a novel regulator of osteoblast activity and suggest LSD1 inhibition as a potential therapeutic target for treatment of osteoporosis.Jun Sun Joerg Ermann Ningning Niu Guang Yan Yang Yang Yujiang Shi Weiguo Zou 2018Bone Research2018,6,3:5
6牛初乳与牛常乳中游离氨基酸和不溶性蛋白质氨基酸对比研究显示文摘牛乳是生产婴幼儿配方乳粉时首要选择的原料乳,氨基酸是构成牛乳蛋白质的结构单位,按照分布区域的不同,分为游离氨基酸和不溶性蛋白质氨基酸两类。以产后0~7 d的牛初乳和15 d~6个月的牛常乳为原料,对牛乳中不同结构域的氨基酸种类及含量进行对比分析。结果表明:9种游离必需氨基酸在牛初乳和牛常乳中均被检测到,分别有8种和7种游离非必需氨基酸在牛初乳和牛常乳中被检测到,其中,牛初乳中8种必需氨基酸、4种非必需氨基酸含量均显著高于牛常乳(P<0.05);在不溶性蛋白质氨基酸中,牛初乳和牛常乳中均含有8种必需氨基酸和10种非必需氨基酸,其中,牛初乳中苏氨酸、精氨酸、丝氨酸、半胱氨酸、丙氨酸含量显著高于牛常乳(P<0.05),而牛常乳中赖氨酸含量显著高于牛初乳(P<0.05)。宋婉莹 李墨翰 张秀敏 杨梅 岳喜庆 郑艳 2021乳业科学与技术2021,44,5:3
7蛋白酶处理对脱脂乳感官品质及游离氨基酸的影响显示文摘以新鲜脱脂牛乳为原料,采用分光测色仪、电子舌及氨基酸自动分析仪等分析酶解处理对脱脂牛乳感官品质、游离氨基酸含量及组成的影响。结果表明:经风味蛋白酶处理的脱脂牛乳水解度高,达到24.61%;蛋白酶处理会导致其感官性状的改变,与脱脂牛乳相比,3种酶解产物L^(*)值均显著(P<0.05)下降,a^(*)(负值)显著上升(P<0.05),风味蛋白酶处理对脱脂牛乳色泽影响大于碱性蛋白酶、复合蛋白酶处理;不同酶解产物滋味轮廓之间存在较大差异,与脱脂牛乳相比其甜味值下降显著,且随酶解时间延长,苦味值上升,甜味值衰退,碱性蛋白酶处理的酶解产物以涩味及涩味回味为主,风味蛋白酶的酶解产物以咸、苦味及苦味回味为主,复合蛋白酶的酶解产物以酸味为主,苦涩等味觉较低,电子舌能较好地区分不同酶解物的滋味差异;酶解处理可使脱脂牛乳中的游离氨基酸及必需氨基酸含量显著增加,苦味氨基酸为主要呈味氨基酸。酶解处理及酶解进程会使脱脂牛乳色泽、滋味及游离氨基酸产生变化,其中风味蛋白酶处理产生的影响大于碱性蛋白酶和复合蛋白酶处理。程娇 孙敬 梁肖娜 钱冠林 岳喜庆 郑艳 2021食品科学2021,42,16:3
8人骨骼肌来源不同表面标志物间充质干细胞特定亚群的多向分化潜能显示文摘背景:骼肌来源的间充质干细胞,在骨形态发生蛋白4等因子的调节下具有多向分化潜能,但具体细胞亚群的分化情况尚不十分明确。目的:观察人骨骼肌来源的不同表面标志物的间充质干细胞特定亚群的多向分化潜能。方法:应用流式细胞分选技术,分选出具有不同细胞表面标志物的人骨骼肌干细胞亚群,根据CD56及CD34/CD144的表达差异,将细胞分成CD56^+,CD56^+CD34^+CD144^+,CD34^+CD144^+及未分选组共4组,对比不同细胞亚群组在骨形态发生蛋白4成骨诱导或骨形态发生蛋白4^+转化生长因子β3成软骨诱导后的差异。通过碱性磷酸酶染色后碱性磷酸酶阳性细胞的百分比评估细胞骨代谢情况。将各亚群细胞进行3D培养和细胞因子处理后,通过硝酸银染色评估其成骨分化程度,通过阿尔新蓝染色评价成软骨分化程度。结果与结论:(1)细胞骨代谢:经骨形态发生蛋白4处理后,4组细胞的碱性磷酸酶阳性细胞的百分比差异无显著性意义(P>0.05);(2)细胞分化:不同表面标记物的4组细胞成骨及成软骨分化有明显差异,在相同成骨培养条件下,CD56^+组成骨能力最强;相同成软骨培养条件下,CD56^+,CD56^+CD34^+CD144^+组呈阿尔新蓝染色阳性,CD56^+CD34^+CD144^+组的染色更深且区域更大;(3)结果证实,成骨与成软骨潜能与不同的人骨骼肌间充质干细胞类型有关。人骨骼肌来源的间充质干细胞CD56^+亚群和成骨潜能有密切关系。同时CD56^+CD34^+CD144^+亚群分化能力更强,具有更强的成软骨潜能。赵亚光 李毅 宋卓悦 李广恒 2017中国组织工程研究2017,21,13:2
9Exosomes derived from human adipose-derived stem cells ameliorate osteoporosis through miR-335-3p/Aplnr axis显示文摘Treatment of osteoporosis is still a challenge in clinic,which leads to an increasing social burden as the aging of population.Exosomes originated from human adipose-derived stem cells(hASCs)hold promise to promote osteogenic differentiation,thus may ameliorate osteoporosis.The main purpose of this study was to investigate the novel usage of hASC-derived exosomes in the treatment of osteoporosis and their underlying mechanism.Two types of exosomes,i.e.,exosomes derived from hASCs cultured in proliferation medium(P-Exos)and osteogenic induction medium(O-Exos),were obtained.As compared with P-Exos,O-Exos could promote the osteogenic differentiation of mouse bone marrow-derived stem cells(mBMSCs)from osteoporotic mice in vitro and ameliorated osteoporosis in vivo.Then,microRNA(miRNA)-335-3p was identified to be the key differentially expressed microRNA between the two exosomes by small RNA sequencing,gene overexpression and knock-down,qRT-PCR,and dual-luciferase reporter assay,and Aplnr was confirmed to be the potential target gene of miRNA-335-3p.In addition,miR335-3p inhibitor-optimized O-Exos were established by transfection of miR-335-3p inhibitor,which significantly enhanced the osteogenic differentiation of mBMSCs in vitro,and bone density and number of trabecular bones in vivo compared with unoptimized O-Exos.Our results indicated that the ASC-exosome-based therapy brings new possibilities for osteoporosis treatment.Besides,engineered exosomes based on transfection of miRNA are a promising strategy to optimize the therapeutic effect of exosomes on osteoporosis.Chunhui Sheng Xiaodong Guo Zhuqing Wan Xiaoqiang Bai Hao Liu Xiao Zhang Ping Zhang Yunsong Liu Wenyue Li Yongsheng Zhou Longwei Lv 2022Nano Research2022,15,10:1
10组蛋白去甲基化酶LSD1结构功能及对干细胞分化调控的研究进展显示文摘间充质干细胞(MSCs)在组织工程、再生医学以及新型药物研发等方面具有重要作用,揭示调控MSCs的定向分化及组织再生效能的分子机制有助于促进MSCs介导的牙颌组织再生。赖氨酸特异性组蛋白去甲基化酶1(LSD1)是第一个被发现的组蛋白去甲基化酶,其在调控细胞转录激活、生理和病理条件下的组蛋白甲基化状态均有重要作用。本文从其在调控干细胞分化方面做一综述,这将有助于进一步研究LSD1调控干细胞分化,为临床干细胞治疗提供理论依据。王利军 郑颖 范志朋 2017口腔生物医学2017,8,2:0
11间充质干细胞成骨向分化的分子调控机制探索显示文摘本文结合文献复习概述了笔者研究团队在间充质干细胞(MSCs)成骨向分化分子调控机制方面的部分探索工作,从表观遗传调控、泛素化修饰、能量代谢三个方面阐述了对MSCs成骨向分化机制的新见解,拓展了基于改善MSCs成骨向分化能力从而促进口腔骨丢失防治和骨组织工程骨再生效果的策略。陆大壮 张萍 周永胜 2022口腔生物医学2022,13,3:0
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