C-type natriuretic peptide stimulates osteoblastic proliferation and collagen-X expression but suppresses fibroblast growth factor-23 expression in vitro

Wei Xia Chen,Fei Fei Liu,Peng Hu,Goshgar Mammadov,Dong Dong Zhang,Sama Samadli,Rui Xue Li,Yang Fang Wu,Hui Hui Liu,Huang Huang Luo,Jing Jing Wang

doi:10.1186/s12969-020-00441-w

Abstract

BackgroundThe effects of C-type natriuretic peptide (CNP) and fibroblast growth factor (FGF)-23 appear to oppose each other during the process of bone formation, whereas few studies exist on the interaction between CNP and FGF-23. The main objective of the present study is to probe whether CNP is directly responsible for the regulation of osteoblast or via antagonizing FGF-23.MethodsOsteoblasts were cultured in the absence or presence of CNP (0, 10, and 100 pmol/L) for 24 h, 48 h and 72 h, respectively.ResultsThe findings of the present study indicated that: (1) CNP significantly stimulated osteoblastic proliferation and collagen (Col)-X expression; (2) both osteoblastic (osteocalcin, procollagen type I carboxy-terminal propeptide, total alkaline phosphatase and bone-specific alkaline phosphatase) and osteolytic (tartrate-resistant acid phosphatase and cross-linked carboxyterminal telopeptide of type I collagen) bone turnover biomarkers were up-regulated by CNP in osteoblasts; (3) FGF-23 mRNA and protein were significantly down-regulated at 24 h by CNP in osteoblasts, but the expression of FGF receptor-1/Klotho had no significant change.ConclusionsCNP stimulates osteoblastic proliferation and Col-X expression via the down-regulation of FGF-23 possibly in vitro. However, the specific mechanisms of the interaction between CNP and FGF-23 in osteoblasts are still unclear according to our findings. A further study on osteoblasts cultured with CNP and FGF-23 inhibitor will be undertaken in our laboratory.

Highlights

C-type natriuretic peptide (CNP) is an endotheliumderived vasodilator and contains two major endogenous forms, designated CNP-53 and CNP-22 [1]
In Nppc−/− mice, the impaired endochondral ossification contributed to early death and severe dwarfism was prevalent in survivals; in contrast, the targeted transgenesis of CNP in the growth plate chondrocytes could rescue the skeletal defect of Nppc−/− mice [13]
CNP promoted the proliferation of osteoblasts Under microscope, active osteoblasts were plump, cuboidal, mononuclear cells lying on the matrix which they synthesized (Fig. 1a)

Summary

Introduction

C-type natriuretic peptide (CNP) is an endotheliumderived vasodilator and contains two major endogenous forms, designated CNP-53 and CNP-22 [1]. The clearance of CNP-22 in human plasma is very rapid, with a calculated half-life of 2.6 min, shorter than that of CNP53 [2, 3] Both of them could result in a significant elevation in intracellular cyclic guanosine monophosphate (cGMP) after selectively binding to the transmembrane natriuretic peptide receptor (NPR)-B [4, 5]. A dramatic impairment of endochondral ossification and an attenuation of longitudinal vertebra or limb-bone growth were found in Npr-b−/− mice, whereas the above skeletal abnormalities could be recovered by Npr-b overexpression [14]. The effects of C-type natriuretic peptide (CNP) and fibroblast growth factor (FGF)-23 appear to oppose each other during the process of bone formation, whereas few studies exist on the interaction between CNP and FGF-23. The main objective of the present study is to probe whether CNP is directly responsible for the regulation of osteoblast or via antagonizing FGF-23

Objectives

Methods

Results

Discussion

Conclusion