c型利钠肽(CNP)和X胶原蛋白标志物(CXM)在骨骼发育不良中异常。

IF 5.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Ricki S Carroll, Robert C Olney, Angela L Duker, Ryan F Coghlan, Andrea J Schelhaas, William G Mackenzie, Colleen P Ditro, Cassondra J Brown, David A O'Connell, William A Horton, Brian Johnstone, Eric A Espiner, Timothy C R Prickett, Michael B Bober
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引用次数: 0

摘要

骨骼发育不良(SD)是一种罕见的影响骨骼发育和骨骼生长的遗传性疾病。尽管在许多情况下已经确定了特定的基因突变,但对导致表型的分子信号通路却知之甚少。c型利钠肽(CNP)信号通路是正常软骨内骨生长的驱动因素,是包括软骨发育不全(最常见的SD)在内的几种骨生长遗传疾病的影响基础。在这项包括7种不同形式的73名SD儿童的横断面研究中,我们检查了生物活性CNP和生物无活性NTproCNP(公认的驱动生长的生物标志物)和胶原X标志物(已建立的生长板反应的生物标志物)的血浆浓度与年龄和年化高度速度(HV)的关系。虽然在一些疾病中发现了与年龄的显著关联,但除了II型胶原疾病和MOPD II外,NTproCNP和胶原X标记物与HV的关联是异常的。在成骨不全症(OI)中,CNP和NTproCNP的减少与OI表型的严重程度成正比。CNP的减少超过NTproCNP,表明OI中生物活性CNP的清除/降解率更高。在OI患者的大范围HV中,生物标志物与HV分离且无关。在其他三种类型的SD(多发性骨骺发育不良、小头性骨增生异常原始性侏儒症II型和Morquio A综合征)中也观察到类似的变化。尽管在同一时间点使用单个样本对每组中有限数量的受影响个体进行了研究,但结果表明,在生物标志物和与HV相关的生物标志物中都存在异常反应。重要的是,我们发现在OI和其他形式的SD中CNP清除率提高,这表明CNP激动剂可能具有治疗益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
C-type natriuretic peptide and collagen X marker are aberrant in skeletal dysplasias.

Skeletal dysplasias (SD) are rare genetic disorders affecting skeletal development and bone growth. Whereas specific gene mutations have been identified in many, however, the molecular signaling pathways contributing to the phenotype are poorly understood. The C-type natriuretic peptide (CNP) signaling pathway is a driver of normal endochondral bone growth and underlies the impact of several genetic disorders of bone growth, including achondroplasia, the most common form of SD. In this cross-sectional study of 73 children with SD, comprising 7 distinct forms, we have examined the association of plasma concentrations of bioactive CNP and bio-inactive NTproCNP (recognized bio markers driving growth) and of collagen X marker (CXM) (an established biomarker of the growth plate response) with age and with annualized height velocity (HV). Although significant associations were identified with age in several disorders, the association of NTproCNP and of CXM with HV was aberrant except in type II collagen disorders and MOPD II. In OI, CNP and NTproCNP were reduced in proportion to severity of OI phenotype. Reduction in CNP exceeded NTproCNP, suggesting that higher rate of clearance/degradation of bioactive CNP occurs in OI. Across a wide range of HV in subjects with OI, biomarkers were dissociated and unrelated to HV. Similar changes were observed in 3 other forms of SD (multiple epiphyseal dysplasia, microcephalic osteodysplastic primordial dwarfism type II, and Morquio A syndrome). Although limited numbers of affected individuals within each group were studied employing a single sample at one time point, the results indicate aberrant responses both within biomarkers and when related to HV. Importantly, we identify enhanced rates of CNP clearance in OI and other forms of SD, which suggests CNP agonists could have therapeutic benefits.

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来源期刊
Journal of Bone and Mineral Research
Journal of Bone and Mineral Research 医学-内分泌学与代谢
CiteScore
11.30
自引率
6.50%
发文量
257
审稿时长
2 months
期刊介绍: The Journal of Bone and Mineral Research (JBMR) publishes highly impactful original manuscripts, reviews, and special articles on basic, translational and clinical investigations relevant to the musculoskeletal system and mineral metabolism. Specifically, the journal is interested in original research on the biology and physiology of skeletal tissues, interdisciplinary research spanning the musculoskeletal and other systems, including but not limited to immunology, hematology, energy metabolism, cancer biology, and neurology, and systems biology topics using large scale “-omics” approaches. The journal welcomes clinical research on the pathophysiology, treatment and prevention of osteoporosis and fractures, as well as sarcopenia, disorders of bone and mineral metabolism, and rare or genetically determined bone diseases.
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