Exogenous C-type natriuretic peptide restores normal growth and prevents early growth plate closure in its deficient rats

• DOI: 10.1371/journal.pone.0204172
• Publication Date: 2018-09-20T17:52:19Z
• Authors: Keisho Hirota; Mayumi Furuya; Naomi Morozumi; Kazunori Yoshikiyo; Takafumi Yotsumoto; Toshimasa Jindo; Ryuichi Nakamura; Koichiro Murakami; Yohei Ueda; Takeshi Hanada; Hiroko Sade; Sayaka Yoshida; Kei Enomoto; Yugo Kanai; Ichiro Yamauchi; Takafumi Yamashita; Yoriko Ueda-Sakane; Toshihito Fujii; Akihiro Yasoda; Nobuya Inagaki
• Keywords: Bone Growth; Endochondral ossification

Signaling by C-type natriuretic peptide (CNP) and its receptor, receptor-B, is a pivotal stimulator of endochondral bone growth. We recently developed CNP knockout (KO) rats that exhibit impaired skeletal growth with early plate closure. In the current study, we further characterized phenotype morphology in CNP-KO rats, effects exogenous rats. used CNP-53, an endogenous form consisting 53 amino acids, administered it for four weeks continuous subcutaneous infusion at 0.15 or 0.5 mg/kg/day to four-week old littermate wild type (WT) demonstrated were useful as reproducible animal model dysplasia, due their impairment There was no significant difference plasma bone-turnover markers between WT At eight age, closure observed distal end tibia calcaneus Continuous CNP-53 significantly, dose-dependent manner, stimulated being more sensitive treatment. also normalized length long bones thickness, prevented Using organ culture experiment fetal rat tibia, gene set enrichment analysis indicated might have negative influence on mitogen activated protein kinase signaling cascades chondrocyte. Our results be valuable investigating physiology mechanism closure, analog, may potential promote prevent short stature.