Tanaka Kiyoshi
College of Nutrition, Koshien University.
Clin Calcium. 2002 Mar;12(3):352-5.
Recently evidence has accumulated that natriuretic peptides (NPs) are important regulator of endochondral ossification. Three peptides, ANP, BNP and CNP constitute the NPs family. cGMP production through two particulate guanylate cyclases is involved in their signal transduction. ANP and BNP have high affinity for GC-A and CNP for GC-B. Third receptor, called clearance receptor (NPR-C) is involved in NPs clearance. Mice that overexpress BNP or CNP and mice deficient in NPR-C exhibited marked body elongation, whereas mice deficient in CNP showed dwarfism. CNP enhanced longitudinal growth in organ-cultured long bones, and stimulated the differentiation of osteoblast and cartilage lineage cells. Dwarfism was observed in mice deficient in cGMP-dependent protein kinase II which lies downstream to cGMP. Since three genetically body-elongated mice were proven to have mutations in NPR-C, it is possible that CNP/GC-B/cGK II pathway is related to some clinical disorders. CNP is also expected to have therapeutic application to diseases with dwarfism.
最近有越来越多的证据表明，利钠肽（NPs）是软骨内骨化的重要调节因子。三种肽，即心房钠尿肽（ANP）、脑钠肽（BNP）和C型钠尿肽（CNP）构成了利钠肽家族。通过两种颗粒型鸟苷酸环化酶产生环磷酸鸟苷（cGMP）参与其信号转导。ANP和BNP对鸟苷酸环化酶-A（GC-A）具有高亲和力，而CNP对鸟苷酸环化酶-B（GC-B）具有高亲和力。第三种受体，称为清除受体（NPR-C），参与利钠肽的清除。过度表达BNP或CNP的小鼠以及缺乏NPR-C的小鼠表现出明显的身体伸长，而缺乏CNP的小鼠则表现出侏儒症。CNP增强了器官培养的长骨的纵向生长，并刺激了成骨细胞和软骨谱系细胞的分化。在位于cGMP下游的依赖cGMP的蛋白激酶II缺乏的小鼠中观察到侏儒症。由于已证实三只基因导致身体伸长的小鼠在NPR-C中有突变，因此CNP/GC-B/cGK II途径可能与某些临床疾病有关。CNP也有望用于治疗侏儒症相关疾病。
