The role of insulin-like growth factor-I in hyaluronan mediated repair of cultured cartilage explants

Objective and Design:To test whether hyaluronan (HA) restores proteoglycan (PG) in fibronectin fragment (Fn-f) damaged cartilage through activities of insulin-like growth factor 1 (IGF-1). Material:Bovine cartilage explants were studied. Methods:Cartilage PG content was measured by a dye binding assay. PG synthesis was measured by incorporation of radiolabeled sulfate. Release of IGF-1 from explants was measured by ELISA. Results:Higher mass HA forms were more reparative than smaller and enhanced PG synthesis in explants, but not in monolayer cultures. Higher mass HA enhanced PG synthesis and retention of IGF-1 within the explants while IGF-1 binding proteins decreased activities of HA. Conclusions:The reparative effects of HA appear to involve enhanced PG synthesis through IGF-1 and requires cartilage matrix.Received 28 July 2003; returned for revision 3 November 2003; accepted by W. B. van den Berg 29 March 2004     

糖痹康对糖尿病模型大鼠坐骨神经胰岛素样生长因子Ⅰ及其受体表达的影响

BACKGROUND: Chinese medicine Tangbikang can improve nerve conduction velocity in diabetic rats, and has anti-inflammatory and antioxidant effects. Insulin like growth factor-I is a key target in the treatment of diabetic peripheral neuropathy. OBJECTIVE: To observe the effect of Tangbikang on the expression of insulin-like growth factor-I and its receptor protein and mRNA in the sciatic nerve of diabetic rat model. METHODS: The experimental diabetes mellitus rat models were induced by feeding high fat forage and injection with streptozotocin. After model establishment, rats were given Tangbikang 4.18, 8.35, 16.7 mg/kg per day. This study set positive control methycobal, model and normal control groups. Intragastric administration was performed for 16 weeks. RESULTS AND CONCLUSION: Compared with the model group, blood glucose levels were similar in the methycobal group, but decreased in the high-dose Tangbikang group (P < 0.01). Immunohistochemical staining and real-time fluorescence quantitative PCR detection revealed that body mass, motor nerve conduction velocity, insulin like growth factor-I and its receptor protein and mRNA expressions were increased in the methycobal and high-dose Tangbikang groups (P < 0.05 or P < 0.01). Results indicated that Tangbikang can prevent and treat diabetic peripheral neuropathy by promoting insulin like growth factor-I and its receptor.       

Role of insulin like growth factor axis in the bleomycin induced lung injury in rats

Background

Alveolar epithelial cell injury has been proposed as a causative factor for the onset and progression of pulmonary fibrosis. However, the role of type II alveolar epithelial cells (AECs) in the epithelial mesenchymal transition (EMT) is controversial.

生长因子用于软骨修复的研究进展

各种原因导致的关节软骨损伤或软骨退行性变是临床的常见病,目前尚缺乏有效的治疗方法.随着组织工程技术的发展,组织工程为软骨损伤修复提供了新的方法.生长因子是软骨组织工程的一个基本要素,近年来已成为软骨修复的研究热点,其在软骨形成和软骨细胞基质的合成、代谢方面发挥重要的作用.本文就转录生长因子-β、骨形态发生蛋白、胰岛素样生长因子等的最新研究做一综述,以期发现理想的生长因子及其组合用于促进软骨修复.     

胰岛素样生长因子-I对体外培养的肾小管上皮细胞表型转化的作用

目的探讨胰岛素样生长因子-I(IGF-I)对体外培养的肾小管上皮细胞(HKC)表型转化的作用及IGF-I和TGF-β1之间有无协同作用。方法分为4组：(1)无血清对照组；(2)阳性对照组TGF-β1(8μg/L)；(3)IGF-I(1、10、50和250μg/L)组；(4)IGF-I(50μg/L) TGF-β1(8μg/L)和IGF-I(250μg/L) TGF-β1(8μg/L)联合作用组。采用免疫荧光和免疫组化双染色法、流式细胞仪和酶联免疫吸附法观察HKC胞质中抗原角蛋白、钙黏蛋白、波形蛋白和α-SMA的表达，检测细胞培养上清液纤连蛋白和型胶原的浓度。结果IGF-I(50、250μg/L)能诱导HKC细胞表达波形蛋白、α-SMA，失去角蛋白和钙黏蛋白的表达；使α-SMA阳性的HKC细胞数显著高于阴性对照组。联合作用组α-SMA阳性的细胞数明显高于IGF-1或TGF-β1单用组，但无协同作用；IGF-I(10、50、250μg/L)组培养上清液纤连蛋白、I型胶原的浓度明显升高，有剂量和时间依赖性。结论IGF-I能诱导肾小管上皮细胞发生表型转化；IGF-I和TGFβ1对诱导HKC转化无协同作用。     

生长因子在关节软骨损伤修复中的应用进展

关节是人体重要的运动器官,其组织结构特殊,成熟关节软骨组织没有血供,一旦损伤难以自愈.临床上常用的关节软骨损伤修复手段有微骨裂术、关节软骨移植、关节置换术、软骨组织工程等,但这些方法的修复效果都不理想.生长因子是体内组织分泌的一种具有生物活性的物质,可促进细胞生长、增殖、迁移和分化.软骨发育过程中有许多生长因子参与,如成纤维细胞生长因子(FGF)、骨形态发生蛋白(BMP)、胰岛素样生长因子(IGF)等.研究显示,在关节软骨修复过程中加入外源性生长因子可有效促进关节软骨损伤的修复.对目前应用于关节软骨损伤修复研究中的生长因子进行综述,讨论这些生长因子在关节软骨发育及其在关节软骨修复中的作用,分析生长因子在关节软骨修复应用中存在的问题.     

Identification of genes required for the spontaneous repair of partial-thickness cartilage defects in immature rats

Purpose: Our previous study showed that partial-thickness articular cartilage defects (PTCDs) created in immature rats spontaneously healed to resemble normal hyaline cartilage, but that of mature rats did not. To identify molecules involved in the spontaneous cartilage repair observed in this model, gene expression was compared between PTCD and sham-operated cartilage of immature and mature rats. Materials and Methods: Six sets of gene comparisons were made at 12, 24, and 48 hours after the creation of PTCDs in immature and mature rats using microarrays. All the genes upregulated in immature cartilage at 12 hours were selected for further analysis if their expression pattern was not irregular such that diminished at 24 hours and re-upregulated at 48 hours. Relationships among genes selected through the above steps were analyzed using Ingenuity Pathway Analysis (IPA) software. After deriving networks, important molecules were further narrowed down by location within a network. Genes were regarded as central if they had relationships with more than 10 molecules in a network. Protein localization in tissues was confirmed by immunohistochemistry. Results: Five networks were identified. Their functional annotations were gene expression, cell cycle, growth and proliferation, and cell signaling. Transforming growth factor-beta (TGF-β) was centrally located in the network with the highest IPA score and mothers against decapentaplegic homolog-3 (Smad3) were centrally located in the second highest ranking network. Phosphorylated Smad3 was detected in the nuclei of chondrocytes in immature cartilage. Conclusions: Our data suggest the possible importance of Smad3 in the TGF-β signaling in the spontaneous healing of PTCDs in immature rats.     

结缔组织生长因子与关节软骨的修复

背景：结缔组织生长因子有刺激间充质细胞向软骨细胞分化的潜能,能促进软骨细胞的增殖和分化,可促进关节软骨细胞Ⅱ型胶原及蛋白多糖的表达,与其他生长因子一起在关节软骨修复的过程中发挥着重要作用。目的：重点就结缔组织生长因子的结构,在关节软骨修复中的功能,与其他物质的相互作用方面作一综述。方法：以“connective tissue growth factor,connective tissue growth factor and articular cartilage,articular cartilage damage,articular cartilage repairment”为英文检索词,以“关节软骨损伤”为中文检索词,检索PubMed数据库、中国知网-cnki数据库1980年1月至2014年7月有关关节软骨损伤修复的文献,排除与软骨损伤的修复重建相关性不强、以及内容重复、陈旧的文献。共保留32篇文献进行综述。结果与结论：结缔组织生长因子有刺激间充质细胞向软骨细胞分化的潜能,能促进软骨细胞的增殖、分化和成熟,可维持胞外基质合成以及平衡,可促进关节软骨细胞Ⅱ型胶原及蛋白多糖的表达,与其他生长因子一起在关节软骨修复的过程中发挥着重要作用。结缔组织生长因子是软骨细胞生长、增殖、分化的关键生长因子之一,贯穿软骨修复整个过程。研究发现,骨性关节炎患者的关节软骨细胞对成纤维细胞生长因子1和结缔组织生长因子表达呈现明显相关性增加。结缔组织生长因子通过对关节软骨组织的信号通路及与其他组织内的细胞因子彼此作用对关节软骨细胞及基质发挥作用。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

软骨形成过程中的转化生长因子β2

背景：转化生长因子β2是一族多肽类生长因子,具有多重生物学效应,对骨髓间充质干细胞增殖分化功能有一定促进作用,是调节骨髓间充质干细胞增殖和向软骨细胞方向分化的最主要因子之一。 目的：探讨转化生长因子β2 的分子结构特点及其在软骨形成方面的作用。 方法：应用计算机检索中国期刊全文数据CNKI、中国期刊全文数据维普中文科技期刊数据库(VIP)和PubMed数据库(1995-01/2011-08)与骨组织工程中转化生长因子β2 诱导软骨形成有关的文章,检索词分别为“转化生长因子β2;软骨细胞分化;骨组织工程”和“TGF-β2;cartilage formation;tissue engineering”。纳入所述内容与转化生长因子β2 分子结构特点,转化生长因子β2信号转导通路,软骨细胞的诱导性分化,软骨性疾病的生物性治疗进展有关。排除综述文献、重复研究、观点陈旧的文章。 结果与结论：初检得到302篇文献,排除262篇不符合标准的文献,共纳入40篇符合标准的文献。经分析得出转化生长因子β2通过促进骨髓间充质干细胞分化为软骨细胞促进软骨特异性基质如Ⅱ型胶原及蛋白多糖的合成,从而发挥软骨诱导作用。转化生长因子β2 与其他因子共同作用调节软骨细胞生长分化,使临床上永久性修复软骨组织缺损的治疗变为可能。     

胰岛素样生长因子结合蛋白-3在脑胶质瘤中的研究进展

胰岛素样生长因子(insulin-like growth factors,IGF)系统包括两种IGF因子、两种IGF因子受体、六种IGF结合蛋白(IGF binding protein,IGFBP)及水解IGFBP的蛋白酶等。IGFBP-3是六种IGF结合蛋白中的一种,目前研究证实IGFBP-3会与相应受体结合形成复合...     

Role of growth factors on periodontal repair

Regeneration of periodontal structures lost during periodontal diseases constitutes a complex biological process regulated among others by interactions between cells and growth factors. Growth factors are biologically active polypeptides affecting the proliferation, chemotaxis and differentiation of cells from epithelium, bone and connective tissue. They express their action by binding to specific cell-surface receptors present on various target cells including osteoblasts, cementoblasts and periodontal ligament fibroblasts. The observation that growth factors participate in all cell functions led to exogenous application during periodontal tissue repair aiming to their use as an alternative therapeutic approach to periodontal therapy. Cell types and cultures conditions, dose, carrier materials, application requirements are of critical importance in the outcome of periodontal repair. The purpose of this article is to review the literature with respect to the biological actions of PDGF, TGF, FGF, IGF and EGF on periodontal cells and tissues, which are involved in periodontal regeneration.     

Role of growth factors on periodontal repair

Regeneration of periodontal structures lost during periodontal diseases constitutes a complex biological process regulated among others by interactions between cells and growth factors. Growth factors are biologically active polypeptides affecting the proliferation, chemotaxis and differentiation of cells from epithelium, bone and connective tissue. They express their action by binding to specific cell-surface receptors present on various target cells including osteoblasts, cementoblasts and periodontal ligament fibroblasts. The observation that growth factors participate in all cell functions led to exogenous application during periodontal tissue repair aiming to their use as an alternative therapeutic approach to periodontal therapy. Cell types and cultures conditions, dose, carrier materials, application requirements are of critical importance in the outcome of periodontal repair. The purpose of this article is to review the literature with respect to the biological actions of PDGF, TGF, FGF, IGF and EGF on periodontal cells and tissues, which are involved in periodontal regeneration.     

胰岛素样生长因子1的免疫调节作用的体外实验研究

目的：探讨胰岛素样生长因子１（ＩＧＦ１） 的免疫调节作用。方法：随机抽取健康个体８２ 名和肿瘤个体１２６ 名,体外提取外周血淋巴细胞后将ＩＬ２ 和或ＩＧＦ１ 共同培养,用３ ＨＴｄＲ 掺入法、３ ＨＴｄＲ 释放法及流式细胞仪检测淋巴细胞增殖活性、杀伤活性和ＣＤ４＋ ＣＤ８＋ 比率。结果：适当浓度的ＩＧＦ１（５０ ｎｇｍｌ）在体外能协同ＩＬ２ 促进ＬＡＫ细胞的增殖,增强其杀伤Ｒａｊｉ细胞的活性,提高淋巴细胞亚群ＣＤ４＋ ＣＤ８＋ 的比率。结论：ＩＧＦ１ 在体外对人体外周血免疫细胞起正向调节作用。     

Bronchial epithelial cells respond to insulin and insulin-like growth factor-I as a chemoattractant

Migration of epithelial cells to cover areas of injury is thought to be important in the repair process following airway insult. Insulin is reported to be a growth factor for bronchial epithelial cells, and growth factors have been known to be chemotactic for many types of cells. Thus, we hypothesized that insulin may be a chemoattractant for bronchial epithelial cells. To evaluate this, we prepared bronchial epithelial cells and measured their chemotactic activity toward insulin. Bronchial epithelial cells were isolated by overnight digestion with bacterial protease, filtered through 100-microns nitex mesh, and then cultured at 1 x 10(6) cells/ml in tissue culture dishes in medium 199 supplemented with transferrin, insulin, epidermal growth factor, hydrocortisone, antibiotics, and 10% FCS for 3 d. The cultured cells were rinsed twice to remove supplements, trypsinized and resuspended at 1 x 10(6) cells/ml in medium 199 without supplements, and used as the cell source for chemotaxis. Chemotactic activity of bronchial epithelial cells was measured by the blindwell chamber technique using 8-microns Nuclepore filter membranes coated with 0.1% gelatin. The cells were added to the top wells in a 48-multiwell chamber with insulin in the bottom wells and incubated for 6 h at 37 degrees C, 5% CO2. Bronchial epithelial cells migrated in response to insulin in a dose-dependent manner up to an optimal dose of insulin, 100 micrograms/ml, and decreased at higher concentrations. The number of migrated cells per 10 high power fields was 33.7 +/- 1.9 at the optimum and 3.7 +/- 0.7 without insulin (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

妊娠期糖尿病与CRP、IGF-1及IGFBP-1相关性研究

目的探讨C反应蛋白（CRP）、胰岛素样生长因子1（IGF-1）与胰岛素样生长因子结合蛋白l（IGFBP-1）在妊娠期糖尿病（GDM）发病中的作用。方法采用免疫透射比浊法和酶联免疫吸附法（ELISA）检测孕24～28周GDM孕妇18例（观察组）和29例正常孕妇（对照组）外周血CRP、IGF-1及IGFBP-1水平,并分析CPR与体重指数、IGF-1与IGFBP-1的相关性。结果（1）两组体重指数（BMI）比较：GDM组（26.01±3.54）kg,较正常组（23.31±2.13）kg高,差异有统计学意义（P〈0.01）;（2）血清CRP水平：GDM组（8.65±5.38）mg/dl,较正常组（5.83±3.26）mg/dl为高,但差异无统计学意义（P〉0.05）;（3）血清IGF-1水平：GDM组（89.16±41.32）ng/ml,正常组（148.95±53.90）ng/ml,两组比较差异有统计学意义（P〈0.01）;（4）血清IGFBP-1水平：GDM组（59.43±10.97）ng/ml较正常组（52.33±9.68）ng/ml高,两组比较差异有统计学意义（P〈0.01）;（5）相关性：血清CRP与体重指数成正相关（r=0.849,P〈0.01）;血清CRP水平与体重指数成正相关,IGF-1与IGFBP-1成负相关（r=-0.33755,P〈0.05）。结论CRP对GDM风险的独立影响不能被证实,但母体血清CRP水平与妊娠期的BMI显著相关,推论肥胖介导的炎症反应导致胰岛素抵抗和糖代谢失调;孕妇外周血IGF-1、IGFBP-1与GDM的发生相关。     

Brain insulin growth factor-I induces diuresis increase through the inhibition of arginin-vasopressin release in aged rats

Normal aging is associated with water homeostasis impairment, arginin-vasopressin (AVP) neuron dysfunction and cerebral insulin growth factor-I (IGF-I) expression deficit. Therefore, we aimed at investigating whether a cerebral chronic treatment of IGF-I in aged rats (26-mo) could restore diuretic function comparable with that observed in adults (3-mo). By using osmotic pumps, we have shown that in aged rats, IGF-I treatment in the third ventricle for four weeks increases water intake and restores diuresis and AVP plasma release similar with that observed in adults. The decrease in AVP plasma release induced by brain IGF-I treatment was also associated with the decrease in urinary osmolality. These results indicate that the age-dependent IGF-I deficit in the brain may be involved in the age-impaired fluid homeostasis in rats.     

组织工程化软骨修复运动性软骨损伤

BACKGROUND: Sports-induced cartilage injury is very common; due to the poor self-healing capacity of the cartilage, cartilage repair has always been a difficult problem. OBJECTIVE: To review the features of different seed cells in tissue-engineered cartilage construction and to explore the application of tissue-engineered cartilage construction in the repair of sports-induced cartilage injury in vitro. METHODS: We searched PubMed database, Wanfang database and CNKI database for articles related to tissue-engineered cartilage repair of sports-induced cartilage injuries, as well as stem cells and scaffold materials used in tissue-engineered cartilage construction. Totally 190 articles were retrieved, and finally 47 articles were included in result analysis after repetitive studies were excluded. RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells under different conditions can differentiate into chondrocytes, and have better potential of chondrogenic differentiation compared with adipose-derived mesenchymal stem cells and umbilical cord-derived mesenchymal stem cells. But, their safety still needs to be further studied. Good scaffolds cannot only induce stem cell differentiation, but also be the key to cartilage construction. Composite materials are the future direction of the scaffold research.      

Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide

Background  

Insulin-like growth factor-I (IGF-I) exerts neuroprotective actions in the central nervous system that are mediated at least in part by control of activation of astrocytes. In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy in reducing the inflammatory response of astrocytes from cerebral cortex.     

关节软骨的修复与修复失败

文题释义： 自体软骨细胞移植：对于3.5-10 cm2的软骨缺损或多个缺损来说,自体软骨细胞移植是一种有效的软骨修复措施,取少量患者自体软骨于体外培养软骨细胞,并增殖到一定数量后植入软骨缺损处,从而达到修复缺损的目的。 基质诱导的自体软骨细胞移植：把经培养增殖后的软骨细胞接种到Ⅰ/Ⅲ型双层胶原膜上,继续培养数日,细胞与支架结合紧密之后,使用生物蛋白胶粘贴到关节软骨缺损病灶底部。术后,软骨细胞从胶原膜上游离并穿过生物胶,迁徙到软骨缺损的基底部。胶原膜和生物胶逐步降解并被吸收。接种的软骨细胞在局部生长、繁殖,并分泌基质,形成新的软骨组织修复缺损。背景：由于关节软骨具有复杂的生物学特性和高度的耐用性,自然退变或创伤引起的缺损都可能导致其结构和功能上不可逆的损害,因此关节软骨损伤后的修复治疗是临床上急需解决的问题。 目的：报告关节软骨修复技术失败最常见的危险因素及其发生率,分析影响选择特定手术治疗方法来处理软骨修复失败最重要的因素。 方法：以“articular cartilage, repair, clinic/clinical failure, surgery”为检索词,检索 PubMed和MEDLINE数据库,时限为2007至2019年,语言限制为英文。初检得到文献约343篇,根据纳入排出标准筛选,共纳入38篇文章进行分析。 结果与结论：①微骨折术和软骨镶嵌成形术在关节软骨修复后的前期和中期显示出不可忽视的失败率,而使用自体软骨细胞移植和异体骨软骨移植修复关节软骨的效果更好。②对于软骨修复失败的治疗：在以往软骨修复失败的患者中应用异体骨软骨移植可能是一个安全的选择,但对于失败的异体骨软骨移植的修复则有更高的失败率;而既往自体软骨细胞移植或基质诱导的自体软骨细胞移植失败的患者,经进一步的自体软骨细胞移植或基质诱导的自体软骨细胞移植治疗后,其治疗效果是可以接受的。此外,有软骨下骨髓刺激病史的患者,自体软骨细胞移植的失败率更高。③软骨修复失败的处理取决于手术治疗失败的类型以及软骨缺损的面积、部位的不同,异体骨软骨移植是治疗软骨下骨髓刺激患者软骨修复失败的最可靠的方法,而自体软骨细胞移植或基质诱导的自体软骨细胞移植在既往软骨修复失败的患者中显示出可以接受的治疗效果,在处理软骨修复失败的患者时,应该特别注意软骨下骨质的情况。ORCID: 0000-0002-3907-9145(张宇) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程