Exogenous C-type natriuretic peptide restores normal growth and prevents early growth plate closure in its deficient rats.
Exogenous C-type natriuretic peptide restores normal growth and prevents early growth plate closure in its deficient rats.
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DOI：
10.1371/journal.pone.0204172
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Inagaki N
中科院分区：
文献类型：
--
作者：
Hirota K;Furuya M;Morozumi N;Yoshikiyo K;Yotsumoto T;Jindo T;Nakamura R;Murakami K;Ueda Y;Hanada T;Sade H;Yoshida S;Enomoto K;Kanai Y;Yamauchi I;Yamashita T;Ueda-Sakane Y;Fujii T;Yasoda A;Inagaki N
c型利钠肽（CNP）及其受体利钠肽受体- b的信号传导是软骨内骨生长的关键刺激物。我们最近开发了CNP敲除（KO）大鼠，这些大鼠表现出骨骼生长受损，早期生长板关闭。在本研究中，我们进一步表征了CNP- ko大鼠的表型和生长板形态，以及外源性CNP对大鼠的影响。我们使用了CNP-53，一种由53个氨基酸组成的内源性CNP，并以0.15或0.5 mg/kg/天的剂量连续皮下输注给4周龄的CNP- ko和同窝野生型（WT）大鼠。由于CNP-KO大鼠软骨内骨生长受损，我们证明CNP-KO大鼠可作为骨骼发育不良的可复制动物模型。血浆骨转换标志物在CNP-KO和WT大鼠之间无显著差异。8周龄时，观察到CNP-KO大鼠胫骨远端和跟骨生长板闭合。持续皮下输注CNP-53显著且呈剂量依赖性地刺激了CNP-KO和WT大鼠的骨骼生长，且CNP-KO大鼠对该治疗更为敏感。CNP-53还能使CNP-KO大鼠长骨长度和生长板厚度正常化，并防止生长板闭合。通过胎鼠胫骨器官培养实验，基因集富集分析表明CNP可能对软骨细胞有丝分裂原激活蛋白激酶信号级联有负面影响。我们的结果表明，CNP-KO大鼠可能是研究生长板生理学和生长板关闭机制的有价值的动物模型，CNP-53或其类似物可能具有促进生长和防止矮小身材早期生长板关闭的潜力。
Signaling by C-type natriuretic peptide (CNP) and its receptor, natriuretic peptide receptor-B, is a pivotal stimulator of endochondral bone growth. We recently developed CNP knockout (KO) rats that exhibit impaired skeletal growth with early growth plate closure. In the current study, we further characterized the phenotype and growth plate morphology in CNP-KO rats, and the effects of exogenous CNP in rats. We used CNP-53, an endogenous form of CNP consisting of 53 amino acids, and administered it for four weeks by continuous subcutaneous infusion at 0.15 or 0.5 mg/kg/day to four-week old CNP-KO and littermate wild type (WT) rats. We demonstrated that CNP-KO rats were useful as a reproducible animal model for skeletal dysplasia, due to their impairment in endochondral bone growth. There was no significant difference in plasma bone-turnover markers between the CNP-KO and WT rats. At eight weeks of age, growth plate closure was observed in the distal end of the tibia and the calcaneus of CNP-KO rats. Continuous subcutaneous infusion of CNP-53 significantly, and in a dose-dependent manner, stimulated skeletal growth in CNP-KO and WT rats, with CNP-KO rats being more sensitive to the treatment. CNP-53 also normalized the length of long bones and the growth plate thickness, and prevented growth plate closure in the CNP-KO rats. Using organ culture experiment of fetal rat tibia, gene set enrichment analysis indicated that CNP might have a negative influence on mitogen activated protein kinase signaling cascades in chondrocyte. Our results indicated that CNP-KO rats might be a valuable animal model for investigating growth plate physiology and the mechanism of growth plate closure, and that CNP-53, or its analog, may have the potential to promote growth and to prevent early growth plate closure in the short stature.
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影响因子：
3.9
作者：
Foldynova-Trantirkova, Silvie;Wilcox, William R.;Krejci, Pavel
通讯作者：
Krejci, Pavel
影响因子：
3.9
作者：
Bocciardi, Renata;Giorda, Roberto;Gimellio, Giorgio
通讯作者：
Gimellio, Giorgio
影响因子：
10.5
作者：
Sahni, M;Ambrosetti, DC;Basilico, C
通讯作者：
Basilico, C
C型纳地尿肽通过p38 MAP激酶依赖性和非依赖性途径调节内软骨的骨生长。
影响因子：
--
作者：
Agoston, Hanga;Khan, Sameena;James, Claudine G.;Gillespie, J. Ryan;Serra, Rosa;Stanton, Lee-Anne;Beier, Frank
通讯作者：
Beier, Frank
影响因子：
2.2
作者：
Shim KS
通讯作者：
Shim KS