Plasma C-Type Natriuretic Peptide: Emerging Applications in Disorders of Skeletal Growth

Espiner, Eric A.; Prickett, Timothy C. R.; Olney, Robert C.

doi:10.1159/000496544

Cited by 15 publications

(13 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In younger rats whose growth plates are thicker, Nppc expression in growth plates would have more impact on the circulating NT-proCNP. Actually in humans, NT-proCNP levels in children are about 2-3 times higher than those in adults [58,59]. Thus our experiments using 4-week-old rats are likely to emphasize the effect of local Nppc change on circulating NT-proCNP.…”

Section: Discussionmentioning

confidence: 79%

Is C-type natriuretic peptide regulated by a feedback loop? A study on systemic and local autoregulatory effect

et al. 2020

View full text Add to dashboard Cite

C-type natriuretic peptide (CNP) is a pivotal enhancer of endochondral bone growth and is expected to be a therapeutic reagent for impaired skeletal growth. Although we showed that CNP stimulates bone growth as a local regulator in the growth plate via the autocrine/paracrine system, CNP is abundantly produced in other various tissues and its blood concentration is reported to correlate positively with growth velocity. Therefore we investigated the systemic regulation of CNP levels using rodent models. In order to examine whether CNP undergoes systemic feedback regulation, we investigated blood CNP levels and local CNP expression in various tissues, including cartilage, of 4-week-old rats after systemic administration of sufficient amounts of exogenous CNP (0.5 mg/kg/day) for 3 days. This CNP administration did not alter blood NT-proCNP levels in male rats but decreased mRNA expression only in tissue that included cartilage. Decrease in expression and blood NT-proCNP were greater in female rats. To analyze the existence of direct autoregulation of CNP in the periphery as an autocrine/paracrine system, we estimated the effect of exogenous supplementation of CNP on the expression of endogenous CNP itself in the growth plate cartilage of extracted fetal murine tibias and in ATDC5, a chondrogenic cell line. We found no alteration of endogenous CNP expression after incubation with adequate concentrations of exogenous CNP for 4 and 24 hours, which were chosen to observe primary and later transcriptional effects, respectively. These results indicate that CNP is not directly autoregulated but indirectly autoregulated in cartilage tissue. A feedback system is crucial for homeostatic regulation and further studies are needed to elucidate the regulatory system of CNP production and function.

show abstract

Section: Discussionmentioning

confidence: 79%

Is C-type natriuretic peptide regulated by a feedback loop? A study on systemic and local autoregulatory effect

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Although we analysed associations in each sex separately, and have eliminated the influence of age (which reduces androgens in both males and females), effects of androgens on relationships of ANP/BNP with risk cannot be excluded but are likely to be small. The possibility that the positive links of NTproCNP with impaired cardiac and metabolic health reflect resistance to the peptide’s actions in tissues 4 – rather than an adaptive response to vascular stress – cannot be excluded. Finally although participants were free of heart disease and were asymptomatic, increase in BNP in some may be due to subtle increases in LV hypertrophy and or end diastolic pressure.…”

Section: Discussionmentioning

confidence: 99%

“…Compared to ANP and BNP, much less is known concerning C-type Natriuretic Peptide (CNP). CNP, acting via its receptor NPR2, is a paracrine/autocrine growth factor which drives postnatal endochondral bone growth 3,4 , has recognised anti-inflammatory and anti-proliferative actions in the vascular intima 5 , and is thought to have important roles in regulating pressure and flow in the microcirculation 6 . CNP is also expressed in myocardial tissues though its contribution to cardiac performance in humans remains unclear 7 .…”

Section: Introductionmentioning

confidence: 99%

Contrasting signals of cardiovascular health among natriuretic peptides in subjects without heart disease

Prickett

Spittlehouse

Miller

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Natriuretic Peptides (NP) are important in maintaining normal cardiac and metabolic status and have been used to predict cardiovascular events. Whether plasma concentrations of NP products within the normal range reflect cardio-metabolic health is unknown. Plasma NTproANP, NTproBNP and NTproCNP and their bioactive counterparts were measured in a random sample of 348 community dwellers aged 49–51 yr without heart disease and associations sought with established vascular risk factors, echocardiographic indices and a genetic variant previously linked with BNP. Stratified by sex, each of ten vascular risk factors were positively associated with NTproCNP whereas associations with NTproBNP and NTproANP were all negative. In both sexes, higher plasma NTproCNP was associated with higher arterial elastance, lower LV stroke volume and lower LV end diastolic volume. Exactly opposite associations were found with plasma NTproBNP or NTproANP. Sex specific differences were identified: positive association of NTproBNP with LV end systolic volume and the negative association with LV elastance were found only in males. The genetic variant rs198358 was independently associated with NTproBNP but not with NTproANP. In conclusion, higher NTproCNP is likely to be an adaptive response to impaired LV relaxation whereas genetic factors likely contribute to higher NTproBNP and improved cardio-metabolic health at midlife.

show abstract

“…Importantly, CNP pathway is one of the possible targets for new treatments in more common dysplasias like achondroplasia. CNP pathway modulation has been used in several experimental studies and clinical trials (Lorget et al, 2012, Espiner et al, 2018, Yotsumoto et al, 2019.…”

Section: Discussionmentioning

confidence: 99%

A new family with epiphyseal chondrodysplasia type Miura

Kenis

Melchenko

Мазунин

et al. 2020

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Epiphyseal chondrodysplasia, Miura type (ECDM) is a skeletal dysplasia with tall stature and distinctive skeletal features caused by heterozygous NPR2 pathogenic variants. Only four families have been reported. We present a family with five affected individuals (mother, three sons, and daughter). The mother's phenotype was relatively mild: borderline tall stature and elongated halluces operated during childhood. The children were remarkably more severely affected with tall stature, scoliosis, and elongated toes and fingers leading to suspicion of Marfan syndrome. Progressive valgus deformities (at the hips, knees, and ankles) were the main complaints and necessitated orthopedic investigations and surgery. Radiographs showed coxa valga, scoliosis, multiple pseudoepiphyses of the fingers and toes with uneven elongation of the digits and ankle valgus. The two older brothers underwent osteotomies and guided growth for axial deformities and arthrodesis for elongated halluces. Genetic testing confirmed the clinical diagnosis of ECDM: all affected individuals had a heterozygous c.2647G>A (p.Val883Met) NPR2 variant in a highly conserved region in the carboxyl‐terminal guanylyl cyclase domain. This two‐generation family elucidates the clinical and radiological variability of the disease. These rare cases are important to gain further understanding of the fundamental processes of growth regulation.

show abstract

Plasma C-Type Natriuretic Peptide: Emerging Applications in Disorders of Skeletal Growth

Cited by 15 publications

References 72 publications

Is C-type natriuretic peptide regulated by a feedback loop? A study on systemic and local autoregulatory effect

Is C-type natriuretic peptide regulated by a feedback loop? A study on systemic and local autoregulatory effect

Contrasting signals of cardiovascular health among natriuretic peptides in subjects without heart disease

A new family with epiphyseal chondrodysplasia type Miura

Contact Info

Product

Resources

About