LRP receptor family member associated bone disease.
LRP receptor family member associated bone disease.
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DOI：
10.1007/s11154-015-9315-2
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发表时间：
2015-06
影响因子：
8.2
通讯作者：
Johnson ML
中科院分区：
文献类型：
--
作者：
Lara-Castillo N;Johnson ML
十几年前，对与两种罕见骨病有关的低密度脂蛋白受体相关蛋白 5 (LRP5) 基因的因果突变的鉴定将骨领域的研究推向了全新的方向。从那时起，强调 Wnt/β-catenin 通路在骨稳态调节中作用的报告数量激增。在这篇综述中，我们讨论了一些最近的报告（过去 2 年），这些报告强调了 LRP 家族成员（LRP5、LRP6、LRP4 和最近的 LRP8）在骨骼维护中的参与及其对骨骼疾病的影响。这些报告包括新的单核苷酸多态性（SNP）和单倍型的记录，表明这些基因的变异可能导致骨骼特征的微妙变化，从而导致极端骨骼表型的突变。所有这些都有助于进一步支持和加强骨骼中这种严格调控途径的重要性。此外，我们还讨论了一些令人兴奋的报告，这些报告提出了通过该途径的抑制剂治疗罕见疾病的新方法，例如骨质疏松症-假性神经胶质瘤综合征（OPPG）、成骨不全症（OI）和硬化症/范布赫姆病。希望通过了解该途径的每个组成部分的作用及其在骨疾病中的参与，这些知识将使我们能够开发新的、更有效的治疗方法，以治疗更常见的疾病，如绝经后骨质疏松症、骨关节炎和类风湿性关节炎以及这些罕见的骨疾病。
A dozen years ago the identification of causal mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene involved in two rare bone disorders propelled research in the bone field in totally new directions. Since then, there have been an explosion in the number of reports that highlight the role of the Wnt/β-catenin pathway in the regulation of bone homeostasis. In this review we discuss some of the most recent reports (in the past 2 years) highlighting the involvement of the members of the LRP family (LRP5, LRP6, LRP4, and more recently LRP8) in the maintenance of bone and their implications in bone diseases. These reports include records of new single nucleotides polymorphisms (SNPs) and haplotypes that suggest variants in these genes can contribute to subtle variation in bone traits to mutations that give rise to extreme bone phenotypes. All of these serve to further support and reinforce the importance of this tightly regulated pathway in bone. Furthermore, we discuss provocative reports suggesting novel approaches through inhibitors of this pathway to treat rarer diseases such as Osteoporosis-Pseudoglioma Syndrome (OPPG), Osteogenesis Imperfecta (OI), and Sclerosteosis/Van Buchem disease. It is hoped that by understanding the role of each component of the pathway and their involvement in bone diseases that this knowledge will allow us to develop new, more effective therapeutic approaches for more common diseases such as post-menopausal osteoporosis, osteoarthritis, and rheumatoid arthritis as well as these rarer bone diseases.