TRANSCRIPTIONAL REGULATION OF OSTEOCALCIN PRODUCTION BY TRANSFORMING GROWTH FACTOR-BETA IN RAT OSTEOBLAST-LIKE CELLS
TRANSCRIPTIONAL REGULATION OF OSTEOCALCIN PRODUCTION BY TRANSFORMING GROWTH FACTOR-BETA IN RAT OSTEOBLAST-LIKE CELLS
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DOI：
10.1210/endo-124-2-612
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发表时间：
1989-02-01
期刊：
影响因子：
4.8
通讯作者：
NODA, M
中科院分区：
文献类型：
--
作者：
NODA, M
骨钙素(OC)是成骨细胞特有的丰富的非胶原性骨基质蛋白之一，其血清水平可作为患者骨代谢的指标。转化生长因子-β。(TGF.beta。)富含骨骼和血小板，促进体内伤口愈合，是成纤维细胞和成骨细胞产生细胞外基质蛋白的有力刺激因子。TGF.beta的作用。在大鼠成骨样细胞ROS17/2.8中检测OC基因的表达。TGF.beta.1使培养液中的OC水平降低2-3倍。TGF.beta.1还以剂量依赖的方式将骨钙素mRNA水平降低约3倍。TGF.beta.2和异二聚体TGF.beta1，2对OC mRNA水平的影响与TGF.beta1相似。OC信使水平在24 h开始受到抑制，并持续到72 h，这种抑制作用可被放线菌酮阻断。TGF.beta1不改变OC mRNA的稳定性。另一方面，根据体外核转录(Run-on)实验估计，OC基因的转录速率降低了4-5倍。TGF.beta1可阻断甲状旁腺激素或1，25-二羟基维生素D3诱导的OC mRNA水平的升高。这些结果表明，TGF.beta。至少部分通过转录调控抑制骨钙素基因的表达。
Osteocalcin (OC) is one of the abundant noncollagenous bone matrix proteins produced exclusively by osteoblasts, and its serum level is used an an indicator of bone metabolism in patients. Transforming growth factor-.beta. (TGF.beta.) is abundant in bones and platelets, promotes wound healing in vivo, and is a potent stimulator of the production of extracellular matrix proteins in fibroblasts and osteoblasts. The effects of TGF.beta. on OC gene expression were examined in rat osteoblast-like cells, ROS17/2.8. TGF.beta.1 decreased OC levels in the culture media 2- to 3-fold. TGF.beta.1 also decreased the level of osteocalcin mRNA about 3-fold in a dose-dependent manner. TGF.beta.2 and TGF.beta.1,2, a heterodimeric form, showed similar effects on OC mRNA levels as TGF.beta.1. The suppression of the OC message level was detectable at 24 h and lasted for up to 72 h. This effect on OC mRNA was blocked by cycloheximide. The stability of OC mRNA was not changed by TGF.beta.1. On the other hand, the rate of OC gene transcription was reduced 4- to 5-fold, as estimated by in vitro nuclear transcription (run-on) assay. TGF.beta.1 blocked the increase in the OC mRNA level induced by PTH or 1,25-dihydroxyvitamin D3. These results indicate that TGF.beta. inhibits osteocalcin gene expression at least in part through transcriptional control.