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

Abstract

Background: 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. Methods: Osteoblasts were cultured in the absence or presence of CNP (0, 10, and 100 pmol/L) for 24 h, 48 h and 72 h, respectively. Results: The 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 upregulated 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. Conclusions: CNP 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.

Circ-AFF2/miR-650/CNP axis promotes proliferation, inflammatory response, migration, and invasion of rheumatoid arthritis synovial fibroblasts

“…Additionally, we further confirmed CNP was a downstream target of miR-650. Multiple evidences suggested CNP had a pro-proliferation role in various cell lines, like melanoma cells, mouse Leydig cells, and osteoblastic cells [ 39 – 41 ]. However, the function of CNP on RAFLS processes remains unclear.…”

C-type natriuretic peptide and its contribution to bone growth

“…Twice, at the beginning and the end of observation, (between 08:00 -10:00 h), blood samples were taken from the antecubital vein and serum was separated. In a part of the serum samples the concentration of 25(OH)D was determined [6]. The remaining samples were stored at -80 °C for further analysis.…”

“…The gene encoding human CNP, named as NPPC (natriuretic peptide precursor C), contains two exons and is located on chromosome 2 (2q37.1) (http://www.genecards.org). Its relatively high level of expression has been detected (among others) in proliferating and pre-hypertrophic chondrocytes of the growth cartilage of the long bones, spine vertebrae, and facial bones [5,6]. The product of the NPPC gene is the 126-amino acid CNP prepropeptide (preproCNP), from which the 103-amino acid CNP propeptide (pro-CNP) is produced with the participation of the serine protease.…”

Molecular Mechanism of Induction of Bone Growth by the C-Type Natriuretic Peptide

“…CNP activation increased the activities of alkaline phosphatase (ALP) and osteocalcin and the mineralization of nodules in the cell culture [ 94 ]. Similarly, CNP upregulated bone turnover biomarkers, both osteoblastic (osteocalcin, procollagen type I, total ALP, and bone-specific alkaline phosphatase) and osteolytic (tartrate-resistant acid phosphatase-TRAP and cross-linked C-terminal telopeptide of type I collagen- CTX-I) in osteoblast-like cells [ 91 ].…”

“…CNP is released by endothelial cells, cardiomyocytes, and fibroblasts and regulates the function of the cardiovascular system together with ANP and BNP [ 86 ]. However, CNP function not only affects the cardiovascular system but also governs bone growth [ 87 , 88 , 89 , 90 , 91 ]. Interestingly, the mechanism of CNP action can be different depending on the cell type.…”