Natriuretic peptide regulation of endochondral ossification - Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway
Natriuretic peptide regulation of endochondral ossification - Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway
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DOI：
10.1074/jbc.273.19.11695
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发表时间：
1998-05-08
影响因子：
4.8
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Yasoda, A;Ogawa, Y;Nakao, K
利钠肽家族包括三种结构相关的内源性配体：心钠素(ANP)、脑利钠肽(BNP)和C型利钠肽(CNP)，利钠肽的生物学作用被认为是通过激活两种鸟苷酸环化酶(GC)偶联的受体亚型(GC-A和GC-B)来实现的。在本研究中，我们利用小鼠胚胎胫骨软骨内成骨模型，研究了分别与GC-A和GC-B相关的内源性配体ANP和CNP对骨生长的影响。与ANP相比，CNP能更有效地促进cGMP的产生，从而导致总纵骨长度的增加。组织学检查显示CNP可使胎鼠胫骨软骨细胞增殖区和肥大区高度增加，8-bromo-cGMP模拟的利钠肽刺激骨生长的作用可被非肽GC偶联的利钠肽受体拮抗剂HS-142-1抑制。HS-142-1可显著抑制小鼠总纵骨生长和cGMP生成的自发增加。CNP在胎鼠胫骨组织中大量表达，但未检测到明显的ANP和BNP基因。胎鼠胫骨中存在相当数量的GC-B基因，提示CNP/GC-B途径在软骨内成骨过程中具有生理学意义。
The natriuretic peptide family consists of three structurally related endogenous ligands: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), The biological actions of natriuretic peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B), In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP, The natriuretic peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-peptide GC-coupled natriuretic peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias, This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.