内分泌
词汇介绍
拓展阅读
解析
Sclerostin
释 义 硬化蛋白
例 句 Moreover, serum levels of sclerostin were significantly lower in patients with AS than in healthy individuals. 而且,AS病人血清硬化蛋白水平显著低于健康人群。
概述
概述
硬化蛋白是人类中由SOST 基因编码的一种蛋白质。硬化蛋白是一种分泌的糖蛋白,具有C端半胱氨酸结样(CTCK)结构域,其序列与骨形态发生蛋白(BMP)拮抗剂DAN(神经母细胞瘤中差异筛选选择的基因异常)家族相似。硬化蛋白主要由骨细胞产生,但也可在其他组织中表达,并且对骨形成具有抗合成代谢作用。
机制
硬化蛋白是SOST基因的产物,位于人的17q12–q21染色体上。最近,硬化蛋白已被鉴定为与LRP5/6受体结合并抑制Wnt信号通路,对Wnt途径的抑制导致减少的骨形成。尽管潜在的机制尚不清楚,但是已经发现硬化蛋白对BMP诱导的骨形成的拮抗作用是由Wnt信号传导介导的,而不是由BMP信号传导途径介导的。硬化素在骨细胞和一些软骨细胞中表达,抑制成骨细胞形成骨。甲状旁腺激素,机械负荷和细胞因子包括前列腺素E2,制抑素M,心肌钙蛋白1和白血病抑制因子抑制骨细胞产生硬化素。降钙素可增加硬化素的产生。因此,成骨细胞的活性由负反馈系统自我调节。
临床应用
编码硬化素蛋白的基因突变与高骨量,硬化症和布赫姆病有关。由于该蛋白对骨骼的特异性,因此正在开发针对硬化蛋白的抗体,在骨质疏松大鼠和猴子的临床前试验中,它的使用增加了骨骼的生长。在一项I期研究中,来自安进公司(Romosozumab)的单剂抗硬化蛋白抗体可增加健康男性和绝经后女性臀部和脊柱的骨密度,并且该药物具有良好的耐受性。在一项II期试验中,骨质疏松妇女一年的抗体治疗比双膦酸盐和特立帕肽治疗增加的骨密度更高;它有轻微的注射副作用。来自礼来公司的硬化蛋白单克隆人类抗体的II期临床试验对绝经后妇女产生积极影响。与安慰剂组相比,每月一次抗体治疗一年可以使脊柱和臀部的骨矿物质密度分别增加18%和6%。在一项 III期试验中,与安慰剂组相比,绝经后妇女接受Romosozumab治疗一年可以减少椎骨骨折的风险。与安慰剂组相比,它还增加了腰椎,股骨颈和全髋的骨矿物质密度,两组之间的不良事件得到了平衡。硬化蛋白在牙科领域具有重要意义,并且针对硬化蛋白的再生策略正在开发中。2019年4月,美国食品药品监督管理局(FDA)批准将罗莫单抗用于骨质疏松性骨折高风险的女性。
血清水平与骨含量和基因表达的比较表明肾移植对硬化蛋白的矛盾作用。
发表时间:2019-11-12
影响指数:8.3
作者: Maria Ju´lia Correia Lima Nepomuceno Arau´jo
期刊:Kidney Int
Kidney transplantation (KTx) has become the treatment of choice for chronic kidney disease (CKD) because it has the potential to improve most of its endocrinological, metabolic, and cardiovascular disorders, increasing life expectancy. However, even after a successful KTx, bone and mineral metabolism might remain compromised; in addition, bone loss, fractures, and persistence of hyperparathyroidism have been described. Post transplantation bone disease is a complex and multifactorial disorder that is influenced by previous CKD-mineral bone disease, as well as immunosuppressive therapy, graft function, and tubular disturbances. Recently new techniques that handle osteocytic bone protein expression have been used in the CKD scenario. A disrupted osteocyte function might lead to abnormal Wnt signaling and play a role in the pathogenesis of renal osteodystrophy through a decrease in bone formation accompanied by an increase in bone resorption. Whereas an increase of both fibroblast growth factor 23 (FGF-23) and sclerostin bone expression has been described in children after transplantation, other studies have shown a decrease in their serum levels after KTx in adults, denoting that little is known about the natural history of the bone expression of these proteins in the CKD population. In this prospective study, we analyzed the expression of proteins related to bone remodeling and to phosphate homeostasis in adult patients with CKD who underwent KTx.
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