Nakayama H, Ichikawa F, Andres J L, Massagué J, Noda M
Department of Molecular Pharmacology, Tokyo Medical University, Japan.
Exp Cell Res. 1994 Apr;211(2):301-6. doi: 10.1006/excr.1994.1091.
Betaglycan (type III transforming growth factor-beta (TGF-beta) receptor) is a cell surface heparan/chondroitin sulfate proteoglycan that binds TGF-beta via its core protein and is abundantly expressed in osteoblastic cells. A previous report (Centrella et al., Mol. Cell. Biol. 11, 4490-4496, 1991) showed post-translational enhancement by glucocorticoid of TGF-beta binding to betaglycan. Upon the availability of the betaglycan cDNA, we investigated the effects of a glucocorticoid analogue, dexamethasone, on the regulation of betaglycan expression in osteoblast-like cells. Betaglycan mRNA was expressed as an approximately 6-kb band in MC3T3-E1 cells. The betaglycan mRNA level was enhanced severalfold by dexamethasone in these cells. The effect of dexamethasone on the betaglycan mRNA level was observed within 9 h and was sustained at least up to 48 h. The dexamethasone effect was dose-dependent, with a saturation concentration at 10(-7) M. Among the steroid hormones examined, dexamethasone exhibited the most potent effect on betaglycan mRNA expression, while retinoic acid also enhanced it moderately. Dexamethasone enhancement of betaglycan mRNA expression was blocked by actinomycin D, but it was not blocked by cycloheximide. Cross-linking experiments showed that dexamethasone treatment increased the binding of radiolabeled TGF-beta 1 to betaglycan, but did not affect binding to the type II receptor. A similar dexamethasone enhancement of betaglycan mRNA expression was also observed in a preosteoblast-like cell line, RCT1. These results suggest that dexamethasone enhances betaglycan expression at least in part via transcriptional events in osteoblasts and this would be one of the target points of glucocorticoid regulation of bone metabolism.
β聚糖（III型转化生长因子-β（TGF-β）受体）是一种细胞表面硫酸乙酰肝素/硫酸软骨素蛋白聚糖，通过其核心蛋白结合TGF-β，在成骨细胞中大量表达。先前的一份报告（Centrella等人，《分子与细胞生物学》11卷，4490 - 4496页，1991年）显示，糖皮质激素可使TGF-β与β聚糖的结合在翻译后增强。在获得β聚糖cDNA后，我们研究了糖皮质激素类似物地塞米松对成骨样细胞中β聚糖表达调控的影响。β聚糖mRNA在MC3T3 - E1细胞中表现为一条约6 kb的条带。地塞米松可使这些细胞中的β聚糖mRNA水平提高数倍。地塞米松对β聚糖mRNA水平的影响在9小时内即可观察到，并且至少持续到48小时。地塞米松的作用呈剂量依赖性，饱和浓度为10^(-7) M。在所检测的甾体激素中，地塞米松对β聚糖mRNA表达的影响最为显著，而视黄酸也能适度增强其表达。放线菌素D可阻断地塞米松对β聚糖mRNA表达的增强作用，但环己酰亚胺不能阻断。交联实验表明，地塞米松处理可增加放射性标记的TGF-β1与β聚糖的结合，但不影响其与II型受体的结合。在成骨前体细胞系RCT1中也观察到了类似的地塞米松对β聚糖mRNA表达的增强作用。这些结果表明，地塞米松至少部分通过成骨细胞中的转录事件增强β聚糖的表达，这可能是糖皮质激素调节骨代谢的靶点之一。
