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骨髓巨核细胞和外周血血小板中存在编码骨钙素的信使核糖核酸,骨钙素是骨转换的标志物。

Presence of messenger ribonucleic acid encoding osteocalcin, a marker of bone turnover, in bone marrow megakaryocytes and peripheral blood platelets.

作者信息

Thiede M A, Smock S L, Petersen D N, Grasser W A, Thompson D D, Nishimoto S K

机构信息

Department of Cardiovascular and Metabolic Diseases, Pfizer, Inc., Groton, Connecticut 06340.

出版信息

Endocrinology. 1994 Sep;135(3):929-37. doi: 10.1210/endo.135.3.8070388.

Abstract

Osteocalcin (Oc), an abundant gamma-carboxylated protein (mol wt, 5800) of bone matrix, is used as a serum marker of bone turnover because it is considered to be uniquely synthesized by the osteoblast. Our finding of Oc messenger RNA (mRNA) in rat tibial diaphyseal marrow led us to investigate the cellular origins of Oc mRNA in peripheral blood and bone marrow. In anticoagulated blood, Oc mRNA was detected in total RNA prepared from buffy coat cells (BCC). Fractionation of rat and human blood showed that platelets contain Oc mRNA identical to that found in bone cells. In rat bone marrow, Oc mRNA is highly enriched in the platelet-producing megakaryocyte population. Depending upon the RIA used, immunoreactive Oc was either undetectable or present at very low levels in platelets and megakaryocytes, suggesting that synthesis of Oc by these cells may be under strong translational regulation. In addition, Oc levels were higher in serum vs. plasma obtained from the same blood, suggesting that Oc may be released by platelets during blood clotting. Interestingly, the magnitude of this difference was greater in female rats. Injection of 1,25-dihydroxyvitamin D3 dose-dependently increased plasma Oc, but did not cause correlative changes in steady state levels of Oc mRNA in BCC. During rat growth, plasma Oc was maximal, whereas Oc mRNA levels in BBC were low. This relationship was reversed during aging. A correlation between Oc mRNA levels in BCC and rat age suggests a developmental regulation of Oc mRNA levels in platelets. These data indicate that Oc mRNA is not restricted to cells on mineralizing surfaces, but is also found in megakaryocytes and peripheral blood platelets, which possibly contribute to the Oc levels in blood and the regulation of bone turnover.

摘要

骨钙素(Oc)是骨基质中一种丰富的γ-羧化蛋白(分子量为5800),由于其被认为是由成骨细胞独特合成的,因此被用作骨转换的血清标志物。我们在大鼠胫骨骨干骨髓中发现了Oc信使核糖核酸(mRNA),这促使我们研究外周血和骨髓中Oc mRNA的细胞来源。在抗凝血中,从血沉棕黄层细胞(BCC)制备的总RNA中检测到了Oc mRNA。对大鼠和人类血液进行分级分离显示,血小板中含有与骨细胞中发现的Oc mRNA相同的物质。在大鼠骨髓中,Oc mRNA在产生血小板的巨核细胞群体中高度富集。根据所使用的放射免疫分析,血小板和巨核细胞中要么检测不到免疫反应性Oc,要么其水平非常低,这表明这些细胞合成Oc的过程可能受到强烈的翻译调控。此外,从同一血液中获得的血清中的Oc水平高于血浆,这表明Oc可能在血液凝固过程中由血小板释放。有趣的是,这种差异在雌性大鼠中更大。注射1,25-二羟基维生素D3剂量依赖性地增加了血浆Oc,但并未引起BCC中Oc mRNA稳态水平的相关变化。在大鼠生长过程中,血浆Oc最高,而BBC中的Oc mRNA水平较低。在衰老过程中这种关系发生了逆转。BCC中Oc mRNA水平与大鼠年龄之间的相关性表明血小板中Oc mRNA水平存在发育调控。这些数据表明,Oc mRNA不仅存在于矿化表面的细胞中,也存在于巨核细胞和外周血血小板中,它们可能对血液中的Oc水平和骨转换的调节有贡献。

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