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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >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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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.

机译：绵羊胎儿骨phy生长板中胰岛素样生长因子（IGFs）和IGF结合蛋白的细胞定位和表达：可能的功能含义。

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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.
机译：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很重要，其作用已被IGF结合蛋白（IGFBPs）调节。因为IGFBPs的解剖分布可能决定了IGF的生物利用度，所以我们使用免疫细胞化学方法和免疫组化方法确定了胎羊骨s生长板中IGF-I，IGF-II和IGFBP-1至IGFBP-6的细胞分布和表达。原位杂交。在生长平板中几乎没有检测到IGF-I的mRNA，但是在生发性和增生性软骨细胞中，IGF-II的mRNA丰富，尽管缺少一些分化的软骨细胞和肥大细胞。 IGF-I和IGF-II的免疫组织化学显示，在包括肥大细胞在内的所有软骨细胞区域中都存在两种肽。免疫反应性IGFBP-2至-5位于软骨细胞的生发和增殖区内，但分化细胞的柱中几乎没有免疫反应性。 IGFBP免疫反应性再次出现在肥大的软骨细胞中。骨phy生长板软骨细胞中的IGFBP mRNA低于原位杂交的可检测极限。然而，通过逆转录酶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能在局部调节IGF的生物利用度和作用。为了检验该假设，从生长板的增殖区建立了软骨细胞的单层培养物，并发现其释放了免疫反应性的IGF-II，并表达了编码IGFBP-2至-6的mRNA。外源IGFBP-3，-4和-5对IGF-II依赖性DNA合成具有抑制作用。 IGFBP-2具有两相作用，在低浓度时可增强IGF-II的作用，但相对于IGF-II，在等摩尔或更高浓度下可抑制DNA合成。与许多IGFBP结合亲和力降低的长R3 IGF-I在促进软骨细胞合成DNA方面比天然IGF-I更有效。我们的发现表明，从循环中产生的局部产生的IGF-II和IGF-I可以影响胎儿骨cho的软骨形成，并且可能受多种IGFBP表达的影响。

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