搜索到362篇“ CHONDROGENESIS“的相关文章
Promoting chondrogenesis by targeted delivery to the degenerating cartilage in early treatment of osteoarthritis
2024年
Osteoarthritis(OA)is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis.The cartilage matrix is mainly composed of collagen,a matrix protein with a hallmark triplehelix structure,which unfolds with collagen degradation on the cartilage surface.A collagen hybridizing peptide(CHP)is a synthetic peptide that binds the denatured collagen triple helix,conferring a potential diseasetargeting possibility for early-stage OA.Here,we constructed an albumin nanoparticle(An)conjugated with CHP,loaded with a chondrogenesis-promoting small molecule drug,kartogenin(KGN).The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA.Compared to treatment with KGN alone,CHP-KGN-An robustly attenuated cartilage degradation,synovitis,osteophyte formation,and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation.Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for earlystage OA therapeutics.
Yuxiang FeiXiaojing LiZhongyang LvZizheng LiuYa XieJiaqi ChenWeitong LiXiyu LiuHu GuoHuan LiuZhaofeng ZhangXunhao WangJingjing FanChunqing HuXiaoyu JinRuiyang JiangNuo XuJiang XiaYang LiDongquan Shi
关键词:COLLAGEN
使用数学模型对髁突颈骨折愈合过程中骨与软骨组织变化的研究
2024年
目的 使用数学模型模拟大鼠髁突颈骨折愈合过程中成骨与成软骨的动态变化过程,探索髁突颈骨折的愈合模式。方法 构建模拟大鼠髁突颈骨折愈合的数学模型,并统计该数学模型28 d内不同时间点生成的各参数(mb, mc, cb和cc)的数值,进而拟合骨、软骨、成骨细胞及成软骨细胞的密度云图和生长曲线并推算成骨方式。结果 数学模型模拟的骨面积比与大鼠骨折实验所测接近(P>0.05)。数学模型模拟的密度云图显示,在骨折后第3天至第7天成骨集中在骨膜周围,在第7天至第21天成骨集中在软骨所在区域并逐渐替代软骨。骨生长曲线与软骨生长曲线在骨折后第5至第8天与第21至第28天正相关,与第8至第14天呈负相关。成骨细胞生长曲线和成软骨细胞生长曲线均呈现先升后降的趋势,成软骨细胞在第6天达到最大密度,成骨细胞则在第13天达到最大密度。结论 数学模型能有效模拟大鼠髁突颈骨折愈合过程,可动态展示该过程中成骨与成软骨的动态变化,为研究髁突颈骨折的愈合方法提供了新思路。
谢春邬琼辉祁峰沈振宇
关键词:数学模型髁突颈骨折骨折愈合骨组织软骨组织
HIF-1α and MIF enhance neutrophil-driven type 3 immunity and chondrogenesis in a murine spondyloarthritis model
2024年
The hallmarks of spondyloarthritis(SpA)are type 3 immunity-driven inflammation and new bone formation(NBF).Macrophage migration inhibitory factor(MIF)was found to be a key driver of the pathogenesis of SpA by amplifying type 3 immunity,yet MIF-interacting molecules and networks remain elusive.Herein,we identified hypoxia-inducible factor-1 alpha(HIF1A)as an interacting partner molecule of MIF that drives SpA pathologies,including inflammation and NBF.HIF1A expression was increased in the joint tissues and synovial fluid of SpA patients and curdlan-injected SKG(curdlan-SKG)mice compared to the respective controls.Under hypoxic conditions in which HIF1A was stabilized,human and mouse neutrophils exhibited substantially increased expression of MIF and IL-23,an upstream type 3 immunity-related cytokine.Similar to MIF,systemic overexpression of IL-23 induced SpA pathology in SKG mice,while the injection of a HIF1A-selective inhibitor(PX-478)into curdlan-SKG mice prevented or attenuated SpA pathology,as indicated by a marked reduction in the expression of MIF and IL-23.Furthermore,genetic deletion of MIF or HIF1A inhibition with PX-478 in IL-23-overexpressing SKG mice did not induce evident arthritis or NBF,despite the presence of psoriasis-like dermatitis and blepharitis.We also found that MIF-and IL-23-expressing neutrophils infiltrated areas of the NBF in curdlan-SKG mice.These neutrophils potentially increased chondrogenesis and cell proliferation via the upregulation of STAT3 in periosteal cells and ligamental cells during endochondral ossification.Together,these results provide supporting evidence for an MIF/HIF1A regulatory network,and inhibition of HIF1A may be a novel therapeutic approach for SpA by suppressing type 3 immunity-mediated inflammation and NBF.
Akihiro NakamuraSungsin JoSayaka NakamuraMansi K.AparnathiShaghayegh Foroozan BoroojeniMariia KorshkoYe-Soo ParkHimanshi GuptaSandra VijayanJason S.RockelMohit KapoorIgor JurisicaTae-Hwan KimNigil Haroon
关键词:INTERLEUKIN-23NEUTROPHILSPONDYLOARTHRITIS
Promotion of osteochondral repair through immune microenvironment regulation and activation of endogenous chondrogenesis via the release of apoptotic vesicles from donor MSCs
2024年
Utilizing transplanted human umbilical cord mesenchymal stem cells(HUMSCs)for cartilage defects yielded advanced tissue regeneration,but the underlying mechanism remain elucidated.Early after HUMSCs delivery to the defects,we observed substantial apoptosis.The released apoptotic vesicles(apoVs)of HUMSCs promoted cartilage regeneration by alleviating the chondro-immune microenvironment.ApoVs triggered M2 polarization in macrophages while simultaneously facilitating the chondrogenic differentiation of endogenous MSCs.Mechanistically,in macrophages,miR-100-5p delivered by apoVs activated the MAPK/ERK signaling pathway to promote M2 polarization.In MSCs,let-7i-5p delivered by apoVs promoted chondrogenic differentiation by targeting the eEF2K/p38 MAPK axis.Consequently,a cell-free cartilage regeneration strategy using apoVs combined with a decellularized cartilage extracellular matrix(DCM)scaffold effectively promoted the regeneration of osteochondral defects.Overall,new mechanisms of cartilage regeneration by transplanted MSCs were unconcealed in this study.Moreover,we provided a novel experimental basis for cell-free tissue engineering-based cartilage regeneration utilizing apoVs.Utilizing transplanted human umbilical cord mesenchymal stem cells(HUMSCs)for cartilage defects yielded advanced tissue regeneration,but the underlying mechanism remain elucidated.Early after HUMSCs delivery to the defects,we observed substantial apoptosis.The released apoptotic vesicles(apoVs)of HUMSCs promoted cartilage regeneration by alleviating the chondro-immune microenvironment.ApoVs triggered M2 polarization in macrophages while simultaneously facilitating the chondrogenic differentiation of endogenous MSCs.Mechanistically,in macrophages,miR-100-5p delivered by apoVs activated the MAPK/ERK signaling pathway to promote M2 polarization.In MSCs,let-7i-5p delivered by apoVs promoted chondrogenic differentiation by targeting the eEF2K/p38 MAPK axis.Consequently,a cell-free cartilage regeneration strategy using apoVs combined with a decel
Guangzhao TianHan YinJinxuan ZhengRongcheng YuZhengang DingZineng YanYiqi TangJiang WuChao NingXun YuanChenxi LiaoXiang SuiZhe ZhaoShuyun LiuWeimin GuoQuanyi Guo
王坚成团队在纳米药物促进干细胞软骨再生治疗骨关节炎研究领域取得新进展
2024年
2024年3月7日,北京大学药学院天然药物及仿生药物全国重点实验室王坚成教授/朱元军博士团队和北京大学第三医院运动医学江东主任医师团队共同在国际学术期刊ACS Nano在线发表了题为“Nanomedicines Promote Cartilage Regeneration in Osteoarthritis by Synergistically Enhancing Chondrogenesis of Mesenchymal Stem Cells and Regulating Inflammatory Environment”的研究论文。该研究提出了碳酸酐酶IX siRNA(siCA9)调控炎症微环境调控促进Kartogenin(KGN)诱导的间充质干细胞(MSCs)软骨定向分化作用的新策略,显著提高了MSCs在骨关节炎(OA)治疗中的软骨再生能力,改善了晚期OA治疗效应。
王坚成王坚成江东
关键词:软骨再生骨关节炎纳米药物干细胞
不同硫酸化程度的糖胺聚糖成软骨作用的体外研究
2023年
目的本研究旨在探讨硫酸软骨素(CS)、硫酸皮肤素(DS)与肝素(HEP)对软骨形成细胞成软骨分化和小鼠关节软骨状态维持的作用及其机制。方法小鼠软骨发生细胞系(ATDC5)和小鼠关节软骨组织块在含不同硫酸化程度糖胺聚糖的培养基中培养后,使用细胞增殖试验、阿利新蓝染色、实时荧光定量聚合酶链反应(RT-qPCR)和蛋白质印迹(Western blot)分析来观察细胞增殖、成软骨分化、软骨形成、软骨组织维持的作用,并进一步探讨其潜在机制。结果HEP和DS主要通过激活骨形态发生蛋白(BMP)信号通路,CS主要通过激活蛋白激酶B(AKT)信号通路促进软骨形成细胞的增殖能力、提高基质蛋白多糖的生成、增加Sox9、Ⅱ型胶原蛋白(Col2a1)和聚集蛋白聚糖(Aggrecan)的表达水平。结论本研究探讨了不同硫酸化程度的糖胺聚糖对细胞成软骨与软骨稳态的维持作用差异及其机制,HEP有助于促进软骨形成和维持软骨组织正常状态,CS在损伤软骨组织再生方面效果更好。
郑雯蔡明详彭荟桢刘敏义刘湘宁
关键词:软骨形成软骨损伤修复
Involvement of Sox9a in chondrogenesis and gonadal development in teleost Nile tilapia(Oreochromis niloticus)被引量:1
2023年
DEAR EDITOR,Sox9 is a member of the Sry-related high-mobility group box(Sox)transcription factor family in animals.In teleost fish,Sox9 undergoes duplication to generate two duplicates,namely Sox9a and Sox9b.However,the functions of these duplicates in the teleost Nile tilapia(Oreochromis niloticus)remain unclear.In this study,we characterized the roles of Nile tilapia Sox9a in chondrogenesis and gonadal development.In situ hybridization assays showed that Sox9a was mainly expressed in cartilage tissues and somatic cells surrounding germ cells of the gonads.CRISPR/Cas9-mediated homozygous mutation of the Sox9a gene resulted in craniofacial deformities and missed mandibles,as well as impaired the expression of Col2a1a that is involved in chondrogenesis.In addition,germ cell number and DNA replication in somatic cells in the gonads of both sexes were reduced following Sox9a mutation.Taken together,this study demonstrates that Sox9a is involved in cartilage development and germ cell proliferation in Nile tilapia.
Xiao-Yan LiYao-Hao TangWan-Yue DengYan ZhengLing-Song WangXue HeQing-Ping XieYue-Qin LiLi DengDe-Shou WangLing Wei
关键词:IMPAIREDSOX9
人脂肪间充质干细胞成软骨分化过程中差异表达长链非编码RNA鉴定及功能
2023年
背景:人脂肪间充质干细胞成软骨分化过程受多种因素影响。研究证实,长链非编码RNAs在表观遗传调控、转录以及转录后水平调控等过程中扮演着重要角色,而目前其在人脂肪间充质干细胞成软骨分化过程中表达谱的改变以及调控作用鲜有报道。目的:探讨人脂肪间充质干细胞成软骨诱导分化过程中差异表达长链非编码RNAs及其功能。方法:以人脂肪间充质干细胞成软骨诱导分化0 d(未诱导组)、14 d(诱导组)细胞为研究对象,利用转录组测序技术筛选成软骨诱导分化前后差异表达倍数变化2倍及以上的长链非编码RNAs和mRNAs,并通过qRT-PCR对测序结果进行验证。采用生物信息学分析对差异表达基因行GO功能分析和KEGG通路富集分析,并筛选长链非编码RNAs邻近基因以及共表达基因。结果与结论:①与未诱导组相比,诱导组中显著差异表达的长链非编码RNAs共有816条,mRNAs共有5138条;②GO功能和KEGG信号通路分析发现,差异表达基因富集的主要生物学过程包括细胞进程、生物调节和代谢过程等;主要通路包括黏附斑激酶、胰岛素信号通路、Wnt信号通路等;③对差异表达长链非编码RNAs行邻近基因和共表达基因分析发现,部分长链非编码RNAs如SNHG16、XLOC_003886可能在脂肪间充质干细胞成软骨分化和软骨退变中发挥重要作用;④结果表明,长链非编码RNA的表达谱在脂肪间充质干细胞诱导成软骨分化过程中发生了明显改变;差异表达长链非编码RNAs的生物学功能可能与邻近基因和共表达基因功能密切相关,从而调控脂肪间充质干细胞成软骨分化。然而,其具体调控作用和分子机制有待实验进一步证实。
孙红邓进彭国璇庄勇刘淼宁旭杨华
关键词:长链非编码RNA脂肪间充质干细胞成软骨分化转录组测序
组织工程医疗产品 用以评价软骨形成的硫酸糖胺聚糖(sGAG)的定量检测
本文件给出了硫酸糖胺聚糖(sulfated glycisaminoglycans,sGAG)的定量检测方法。本文件适用于关节软骨、半月板、弹性软骨、组织工程软骨的细胞外基质中sGAG含量检测。
魏利娜杨晓琴张乐李娜梁洁徐丽明
载姜黄素电纺膜包裹模式维持干细胞再生软骨体内稳定性的实验研究
2023年
目的探索载姜黄素电纺膜包裹模式用于维持干细胞再生软骨体内稳定性的可行性。方法将具有抗血管化作用的姜黄素与聚L-丙交酯-己内酯(PLCL)混合,并采用静电纺丝技术制备载姜黄素PLCL电纺膜,以单纯PLCL电纺膜作为对照组,行大体观及扫描电镜观察其表面形貌。随后在体外与人脐静脉血管内皮细胞共培养6 h,以探究载姜黄素PLCL电纺膜抗血管生成能力。另外,取兔骨髓间充质干细胞(BMSC)接种于明胶多孔支架,经体外成软骨诱导培养3周后,行大体及组织学检测以验证再生软骨组织。最后,将载姜黄素PLCL电纺膜紧密封装BMSC再生软骨组织,并植入裸鼠皮下培养6周后,行大体观察、Micro-CT及组织学检测,观察BMSC再生软骨的骨化及稳定软骨表型情况。结果有别于白色的PLCL电纺膜,载姜黄素PLCL电纺膜呈黄色大体观,但两者具有相似的纳米纤维样结构。体外血管形成实验表明,相较于PLCL电纺膜,载姜黄素PLCL电纺膜具有显著的抗血管生成能力。体外成软骨诱导实验表明,BMSC-明胶支架呈软骨样大体观,HE染色显示软骨陷窝结构及软骨特异性细胞外基质分泌,番红O染色证实有蛋白聚糖基质产生。裸鼠体内实验表明,PLCL组出现明显的血管入侵,而载姜黄素PLCL组无肉眼可见的血管入侵。Micro-CT图像显示PLCL组出现大量骨小梁组织,而载姜黄素PLCL组仅出现极少的骨小梁结构。HE及番红-固绿染色进一步证实PLCL组具有大量典型的骨小梁结构和典型骨特异性细胞外基质,而载姜黄素PLCL组为典型的陷窝结构及软骨特异性细胞外基质。结论载姜黄素电纺膜包裹模式可以有效维持干细胞再生软骨的体内稳定性。
胡豆豆徐勇贾维
关键词:姜黄素抗血管生成骨化

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供职机构:上海交通大学附属第六人民医院
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