Dexamethasone stimulates expression of C-type Natriuretic Peptide in chondrocytes.
Dexamethasone stimulates expression of C-type Natriuretic Peptide in chondrocytes.
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DOI：
10.1186/1471-2474-7-87
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发表时间：
2006-11-20
影响因子：
2.3
通讯作者：
Beier F
中科院分区：
文献类型：
--
作者：
Agoston H;Baybayan L;Beier F
软骨内骨的生长通过软骨生长板的活动来调节。软骨细胞增殖和分化的生理模式的破坏-例如在内分泌紊乱或许多不同的遗传疾病（例如软骨发育不良）中-通常导致侏儒症和骨骼缺陷。例如，儿童使用糖皮质激素会抑制软骨内骨的生长，但这些激素在软骨细胞中的分子靶点仍然很大程度上未知。相比之下，最近的研究表明，C型利钠肽（CNP）是软骨生长的重要合成代谢调节剂，而人CNP受体基因的功能缺失突变导致侏儒症。我们询问糖皮质激素是否可以通过干扰CNP或其下游信号组分的表达来发挥其活性。将单层的原代小鼠软骨细胞与合成糖皮质激素地塞米松（DEX）孵育12至72小时。通过计数确定细胞数量，并进行实时PCR以检查DEX对CNP信号通路中基因的调节。我们发现DEX确实影响CNP通路中关键基因的表达。最重要的是，DEX显著增加编码CNP本身的基因（Nppc）的RNA表达。此外，DEX刺激Prkg 2（编码cGMP依赖性蛋白激酶II）和Npr 3（利钠肽诱饵受体）基因的表达。相反，发现DEX下调编码其受体Nr 3c 1（糖皮质激素受体）的基因以及Npr 2基因（编码CNP受体）的表达。我们的数据表明DEX的生长抑制活性不是由于CNP信号传导的阻断。这项研究揭示了糖皮质激素和CNP信号传导之间的一种新的，意想不到的关系，并提供了第一个证据表明，软骨细胞中的CNP表达是由内分泌因子调节。
Growth of endochondral bones is regulated through the activity of cartilaginous growth plates. Disruption of the physiological patterns of chondrocyte proliferation and differentiation – such as in endocrine disorders or in many different genetic diseases (e.g. chondrodysplasias) – generally results in dwarfism and skeletal defects. For example, glucocorticoid administration in children inhibits endochondral bone growth, but the molecular targets of these hormones in chondrocytes remain largely unknown. In contrast, recent studies have shown that C-type Natriuretic Peptide (CNP) is an important anabolic regulator of cartilage growth, and loss-of-function mutations in the human CNP receptor gene cause dwarfism. We asked whether glucocorticoids could exert their activities by interfering with the expression of CNP or its downstream signaling components. Primary mouse chondrocytes in monolayer where incubated with the synthetic glucocorticoid Dexamethasone (DEX) for 12 to 72 hours. Cell numbers were determined by counting, and real-time PCR was performed to examine regulation of genes in the CNP signaling pathway by DEX. We show that DEX does influence expression of key genes in the CNP pathway. Most importantly, DEX significantly increases RNA expression of the gene encoding CNP itself (Nppc). In addition, DEX stimulates expression of Prkg2 (encoding cGMP-dependent protein kinase II) and Npr3 (natriuretic peptide decoy receptor) genes. Conversely, DEX was found to down-regulate the expression of the gene encoding its receptor, Nr3c1 (glucocorticoid receptor), as well as the Npr2 gene (encoding the CNP receptor). Our data suggest that the growth-suppressive activities of DEX are not due to blockade of CNP signaling. This study reveals a novel, unanticipated relationship between glucocorticoid and CNP signaling and provides the first evidence that CNP expression in chondrocytes is regulated by endocrine factors.
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影响因子：
9.5
作者：
Kuhn, M
通讯作者：
Kuhn, M
影响因子：
3.6
作者：
Mericq, V;Uyeda, JA;Baron, J
通讯作者：
Baron, J
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4.8
作者：
Rahmutula, D;Gardner, DG
通讯作者：
Gardner, DG
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4.8
作者：
Miyazawa, T;Ogawa, Y;Nakao, K
通讯作者：
Nakao, K
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4.8
作者：
Chrysis, D;Zaman, F;Sävendahl, L
通讯作者：
Sävendahl, L