Cellular localization and expression of insulin-like growth factors (IGFs) and IGF binding proteins within the epiphyseal growth plate of the ovine fetus: possible functional implications.
Cellular localization and expression of insulin-like growth factors (IGFs) and IGF binding proteins within the epiphyseal growth plate of the ovine fetus: possible functional implications.
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绵羊胎儿骨骺生长板内胰岛素样生长因子 (IGF) 和 IGF 结合蛋白的细胞定位和表达：可能的功能意义。
DOI：
10.1139/y99-015
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发表时间：
1999
影响因子：
2.1
通讯作者：
D. J. Hill
中科院分区：
文献类型：
--
作者：
P. De Los Rios;D. J. Hill
胰岛素样生长因子（IGFs）在正常胎儿肌肉骨骼生长和发育的调节中是重要的，并且它们的作用已被证明是由IGF结合蛋白（IGFBPs）调节的。由于IGFBPs的解剖学分布可能决定IGF的生物利用度，因此我们使用免疫细胞化学和原位杂交法测定了胎羊骺生长板中IGF-I、IGF-II和IGFBP-1至IGFBP-6的细胞分布和表达。在生长板内检测到很少的IGF-Ⅰ mRNA，但IGF-Ⅱ mRNA在生发和增殖的软骨细胞中丰富，尽管在一些分化的软骨细胞和肥大细胞中不存在。IGF-I和IGF-II的免疫组织化学显示，在所有软骨细胞区，包括肥大细胞的存在下，这两种肽。免疫反应性IGFBP-2至-5定位于软骨细胞的生发区和增殖区，但分化细胞列内几乎没有免疫反应性。IGFBP免疫反应再次出现在肥大的软骨细胞。骨骺生长板软骨细胞IGFBPmRNA低于原位杂交的检测限。然而，通过逆转录聚合酶链反应检测到IGFBP-2至-6的mRNA水平较低。IGFBPs与IGF肽在完整软骨中的共定位表明它们可以局部调节IGF的生物利用度和作用。为了验证这一假设，从生长板的增殖区建立软骨细胞的单层培养物，发现其释放免疫反应性IGF-II并表达编码IGFBP-2至-6的mRNA。外源性IGFBP-3、-4和-5对IGF-II依赖的DNA合成具有抑制作用。IGFBP-2具有双相效应，在低浓度下增强IGF-II的作用，但在等摩尔或更高浓度下抑制DNA合成。长R3 IGF-I对许多IGFBPs的结合亲和力降低，在促进软骨细胞DNA合成方面比天然IGF-I更有效。我们的研究结果表明，局部产生的IGF-II和IGF-I来自循环可以影响胎儿骺软骨的形成，这可能是由多个IGFBP表达局部调制。
The insulin-like growth factors (IGFs) are important in the regulation of normal fetal musculoskeletal growth and development, and their actions have been shown to be modulated by IGF binding proteins (IGFBPs). Because the anatomical distribution of IGFBPs is likely to dictate IGF bioavailability, we determined the cellular distribution and expression of IGF-I, IGF-II, and IGFBP-1 to IGFBP-6 in epiphyseal growth plates of the fetal sheep, using immunocytochemistry and in situ hybridization. Little mRNA for IGF-I was detectable within the growth plates, but mRNA for IGF-II was abundant in germinal and proliferative chondrocytes, although absent from some differentiating chondrocytes and hypertrophic cells. Immunohistochemistry for IGF-I and IGF-II showed a presence of both peptides in all chondrocyte zones, including hypertrophic cells. Immunoreactive IGFBP-2 to -5 were localized within the germinal and proliferative zones of chondrocytes, but little immunoreactivity was present within the columns of differentiating cells. IGFBP immunoreactivity again appeared in hypertrophic chondrocytes. IGFBP mRNA in chondrocytes of the epiphyseal growth plate was below the detectable limit of in situ hybridization. However, low levels of mRNAs for IGFBP-2 to -6 were detected by the reverse transcriptase polymerase chain reaction. A co-localization of IGFBPs with IGF peptides in intact cartilage suggests that they may regulate IGF bioavailability and action locally. To test this hypothesis, monolayer cultures of chondrocytes were established from the proliferative zone of the growth plate, and were found to release immunoreactive IGF-II and to express mRNAs encoding IGFBP-2 to -6. Exogenous IGFBP-3, -4, and -5 had an inhibitory action on IGF-II-dependent DNA synthesis. IGFBP-2 had a biphasic effect, potentiating IGF-II action at low concentrations but inhibiting DNA synthesis at equimolar or greater concentrations relative to IGF-II. Long R3 IGF-I, which has a reduced binding affinity for many IGFBPs, was more potent than native IGF-I in promoting DNA synthesis by chondrocytes. Our findings suggest that locally produced IGF-II and IGF-I derived from the circulation can influence fetal epiphyseal chondrogenesis, and that this may be modulated locally by multiple IGFBP expression.
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影响因子：
20.3
作者：
John I. Jones;D. Clemmons
通讯作者：
John I. Jones;D. Clemmons
25 千道尔顿胰岛素样生长因子 (IGF) 结合蛋白在体外抑制鸡胚骨盆软骨的基础生长和 IGF-I 介导的生长。
DOI：
10.1210/jcem-70-1-173
发表时间：
1990
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Burch,WM;Correa,J;Shively,JE;Powell,DR
通讯作者：
Powell,DR
内皮细胞表达胰岛素样生长因子结合蛋白 2 至 6。
DOI：
10.1210/mend.6.11.1282670
发表时间：
1992
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Moser,DR;LoweJr,WL;Dake,BL;Booth,BA;Boes,M;Clemmons,DR;Bar,RS
通讯作者：
Bar,RS
人成骨细胞内源性胰岛素样生长因子结合蛋白5的调控及生物学效应。
DOI：
10.1210/jcem.76.5.7684391
发表时间：
1993
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Conover,CA;Kiefer,MC
通讯作者：
Kiefer,MC