C-type natriuretic peptide attenuates renal osteodystrophy through inhibition of FGF-23/MAPK signaling

Zhang, Dong Dong; Wu, Yang; Chen, Wei Xia; Xu, Yao; Liu, Si Yan; Luo, Huang Huang; Jiang, Guang Mei; Wu, Yue; Hu, Peng

doi:10.1038/s12276-019-0265-8

Cited by 6 publications

(7 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over the past two decades, increasing evidence has demonstrated CNP importance as a physiological stimulator of longitudinal bone growth, chondrocytic proliferation and hypertrophy, and cartilage matrix synthesis [9,25]. Pathologically, our latest study established a rat model of renal osteodystrophy and observed that CNP administration significantly restored calcium phosphate metabolic disorders, hypovitaminosis D, secondary hyperparathyroidism and decreased bone turnover markers, and retarded bone pathological progression [26]. To eliminate disturbance from the neuroendocrine network, the present study cultured osteoblasts with different doses of CNP and found that osteoblastic proliferation could be directly promoted by exogenous CNP in a dose-dependent manner in vitro.…”

Section: Discussionmentioning

confidence: 98%

“…Moreover, identical results were obtained using the chondrogenic cell line ATDC5. In our previous study, we established a renal osteodystrophy rat model to identify whether CNP could attenuate renal osteodystrophy through the inhibition of FGF-23 cascades, and found that a continuous infusion of CNP (0.05 μg/kg/min × 1 h) significantly inhibited the expression of FGF-23, RAF-1/phospho-RAF-1, and downstream ERK/phospho-ERK in bone tissue [26]. As for FGF-23 signaling, no dose effect of CNP was observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Chen

Liu

et al. 2020

Pediatr Rheumatol

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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

Chen

Liu

et al. 2020

Pediatr Rheumatol

Self Cite

View full text Add to dashboard Cite

show abstract

“…NPR-B expression in the PT suggests CNP as a regulator of tubular transport in this nephron segment, which is compatible with previous results in NPR-B knockout mice that have impaired diuresis and developed salt-dependent renal injury [ 28 ]. Because of the nephroprotective potential of CNP, observed in various animal experiments, the expression of NPR-B in the PT might exert a primary protective function [ 9 , 28 , 77 ]. Interestingly, marked protective effects of CNP treatment was observed in models with primary damage of proximal tubules, such as cisplatin-induced nephrotoxicity, ischemia/reperfusion or hemorrhagic shock [ 8 , 28 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Localization of natriuretic peptide receptors A, B, and C in healthy and diseased mouse kidneys

Heinl

Broeker

Lehrmann

et al. 2022

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

The natriuretic peptides (NPs) ANP (atrial natriuretic peptide) and BNP (B-type natriuretic peptide) mediate their widespread effects by activating the natriuretic peptide receptor-A (NPR-A), while C-type natriuretic peptide (CNP) acts via natriuretic peptide receptor-B (NPR-B). NPs are removed from the circulation by internalization via the natriuretic peptide clearance receptor natriuretic peptide receptor-C (NPR-C). In addition to their well-known functions, for instance on blood pressure, all three NPs confer significant cardioprotection and renoprotection. Since neither the NP-mediated renal functions nor the renal target cells of renoprotection are completely understood, we performed systematic localization studies of NP receptors using in situ hybridization (RNAscope) in mouse kidneys. NPR-A mRNA is highly expressed in glomeruli (mainly podocytes), renal arterioles, endothelial cells of peritubular capillaries, and PDGFR-receptor β positive (PDGFR-β) interstitial cells. No NPR-A mRNA was detected by RNAscope in the tubular system. In contrast, NPR-B expression is highest in proximal tubules. NPR-C is located in glomeruli (mainly podocytes), in endothelial cells and PDGFR-β positive cells. To test for a possible regulation of NPRs in kidney diseases, their distribution was studied in adenine nephropathy. Signal intensity of NPR-A and NPR-B mRNA was reduced while their spatial distribution was unaltered compared with healthy kidneys. In contrast, NPR-C mRNA signal was markedly enhanced in cell clusters of myofibroblasts in fibrotic areas of adenine kidneys. In conclusion, the primary renal targets of ANP and BNP are glomerular, vascular, and interstitial cells but not the tubular compartment, while the CNP receptor NPR-B is highly expressed in proximal tubules. Further studies are needed to clarify the function and interplay of this specific receptor expression pattern.

show abstract

“…MaPK signaling pathway has been recognized as an important regulator of osteoblast differentiation and bone mass (49,50). The upstream stimulation can activate the key components of the MaPK signaling pathway by Protein expression of Runx2 and OSX in the control, Ti, JNK inhibitor and Ti + JNK inhibitor groups were measured.…”

Section: Discussionmentioning

confidence: 99%

Role of MAPK/JNK signaling pathway on the regulation of biological behaviors of MC3T3‑E1 osteoblasts under titanium ion exposure

et al. 2020

View full text Add to dashboard Cite

The oral cavity is a complex environment that is constantly undergoing remodeling. This provides a favorable electrolytic aqueous condition, which causes the corrosion of titanium implants and the release of titanium (Ti) ions. The accumulation of Ti ions in the peri-implant tissues may affect the osteogenesis process. Therefore, the present study aimed to investigate the possible effects of Ti ions on osteoblast physiology and its underlying mechanism, specifically the MaPK/JnK signaling pathway. in the present study, Mc3T3-e1 osteoblasts were cultured the medium containing 10 ppm Ti ions. confocal laser scanning microscopy was used to analyze cell morphology and adhesion. alkaline phosphatase (alP) activity assay and western blotting were performed to evaluate the expression of proteins associated with osteogenesis such as runx2 and osterix. nuclear translocation of JnK, a key factor of the MaPK signaling pathway, was visualized and analyzed using immunofluorescence staining. The results showed that 10 ppm Ti ions exerted negative effects on the biological behaviors of Mc3T3-e1 cells, which exhibited reduced adhesion, alP activity and osteogenic differentiation. it was also found that 10 ppm Ti ions activated the MaPK/JnK signaling pathway by promoting the nuclear translocation of JnK via phosphorylation. in addition, the inhibitory effects of 10 ppm Ti ions on Mc3T3-e1 cells was found to be reversed by the JnK inhibitor SP600125. in conclusion, the preset study suggests that the MaPK/JnK signaling pathway serves a key role in the molecular mechanism underlying the changes in osteoblast behavior following Ti ion exposure. These findings may serve as a valuable reference point for the further in-depth exploration of peri-implant bone loss.

show abstract

C-type natriuretic peptide attenuates renal osteodystrophy through inhibition of FGF-23/MAPK signaling

Cited by 6 publications

References 53 publications

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

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

Localization of natriuretic peptide receptors A, B, and C in healthy and diseased mouse kidneys

Role of MAPK/JNK signaling pathway on the regulation of biological behaviors of MC3T3‑E1 osteoblasts under titanium ion exposure

Contact Info

Product

Resources

About