Gabbitas B, Canalis E
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105-1299, USA.
J Cell Physiol. 1997 Aug;172(2):253-64. doi: 10.1002/(SICI)1097-4652(199708)172:2<253::AID-JCP12>3.0.CO;2-A.
Insulin-like growth factors (IGF) I and II are the most abundant growth factors secreted by skeletal cells, and retinoic acid has many important action on cell differentiation and osteoblastic function. Some of these actions may be mediated by changes in the expression of IGF I and II since IGFs are known to enhance the differentiated function of the osteoblast. We examined the effects of all-transretinoic acid on IGF I and IGF II expression in cultures of osteoblast-enriched cells from 22 day fetal rat calvariae (Ob cells). Retinoic acid caused a transient increase in IGF I and IGF II mRNA levels after 6 h, but after 24 and 48 h of treatment a dose-dependent decrease was observed. Cycloheximide prevented the inhibitory effect of retinoic acid. Retinoic acid treatment for 48 h decreased IGF I polypeptide levels in the culture medium. In contrast, 48 h exposure to retinoic acid increased IGF II polypeptide levels, possible due to increased levels of IGF binding protein-6. The decay of IGF I and II mRNA in transcriptionally arrested Ob cells was similar in control and retinoic acid-treated cells. After 2 h, retinoic acid increased the rates of IGF I and II transcription, as determined by a nuclear run-on assay and heterogeneous nuclear RNA levels, but after 24 h retinoic acid was inhibitory. Retinoic acid had opposite effects to IGFs in osteoblasts and inhibited DNA and collagen synthesis. In conclusion, following a small transient increase, retinoic acid causes a pronounced decrease in IGF I and IGF II mRNA expression in Ob cells. However, treatment with retinoic acid causes a decrease in IGF I and an increase in IGF II polypeptide levels. These changes in the IGF/IGFBP axis may be relevant to the mechanism of action of retinoic acid in bone.
胰岛素样生长因子（IGF）Ⅰ和Ⅱ是骨骼细胞分泌的最丰富的生长因子，视黄酸对细胞分化和成骨细胞功能有许多重要作用。其中一些作用可能是由IGFⅠ和Ⅱ表达的变化介导的，因为已知IGF可增强成骨细胞的分化功能。我们研究了全反式视黄酸对来自22日龄胎鼠颅骨的富含成骨细胞的培养物（成骨细胞）中IGFⅠ和IGFⅡ表达的影响。视黄酸在6小时后导致IGFⅠ和IGFⅡ mRNA水平短暂升高，但在处理24小时和48小时后观察到剂量依赖性降低。放线菌酮可防止视黄酸的抑制作用。视黄酸处理48小时可降低培养基中IGFⅠ多肽水平。相反，暴露于视黄酸48小时可增加IGFⅡ多肽水平，这可能是由于IGF结合蛋白-6水平升高所致。在转录停滞的成骨细胞中，IGFⅠ和Ⅱ mRNA的衰减在对照细胞和视黄酸处理的细胞中相似。2小时后，视黄酸增加了IGFⅠ和Ⅱ的转录速率，这通过核延伸试验和不均一核RNA水平测定，但是在24小时后视黄酸具有抑制作用。视黄酸在成骨细胞中对IGF有相反的作用，并抑制DNA和胶原蛋白合成。总之，在短暂的小幅度升高之后，视黄酸导致成骨细胞中IGFⅠ和IGFⅡ mRNA表达明显降低。然而，视黄酸处理导致IGFⅠ降低而IGFⅡ多肽水平升高。IGF/IGFBP轴的这些变化可能与视黄酸在骨骼中的作用机制有关。
