Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A.
Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A.
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DOI：
10.3389/fendo.2018.00031
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发表时间：
2018
影响因子：
5.2
通讯作者：
Oxvig C
中科院分区：
文献类型：
--
作者：
Beattie J;Al-Khafaji H;Noer PR;Alkharobi HE;Alhodhodi A;Meade J;El-Gendy R;Oxvig C
胰岛素样生长因子（IGF）轴是骨组织分化、发育和维持所必需的。因此，该轴的失调与包括生长异常和受损骨结构的各种骨骼病理学相关。越来越明显的是，必须从整体上看待IGF轴的作用，不仅要考虑生长因子和受体的作用，而且可溶性高亲和力IGF结合蛋白（IGFBPs）的影响。IGFBPs在骨和其他组织中的独立作用，了解IGFBPs的作用机制及其在细胞周围环境中的调节对组织的影响至关重要。physiology.在这方面，一组IGFBP蛋白酶（可被认为是IGF轴的辅助成员）在调节IGFBP功能中起着至关重要的作用。在该模型中，特异性蛋白酶将IGFBP切割成对生长因子具有较低亲和力的片段，调节IGFBP和细胞表面IGF受体之间IGF的分配。在这篇综述中，我们研究了IGFBP功能在骨组织中的重要性，特别强调了妊娠相关血浆蛋白-A（PAPP-A）的作用。我们研究了PAPP-A主要作为IGFBP-4蛋白酶的功能，并提出证据表明PAPP-A诱导的IGFBP-4裂解可能是骨代谢的关键调节步骤。我们还强调了一些关于IGFBP-2和IGFBP-5（也是PAPP-A底物）在骨组织中功能的最新发现，并简要讨论了其他三种IGFBP（-1，-3和-6）在该组织中的作用。虽然我们的主要重点将在骨，我们将暗示IGFBP在其他细胞和组织中的活性在适当的情况下。
The insulin-like growth factor (IGF) axis is required for the differentiation, development, and maintenance of bone tissue. Accordingly, dysregulation of this axis is associated with various skeletal pathologies including growth abnormalities and compromised bone structure. It is becoming increasingly apparent that the action of the IGF axis must be viewed holistically taking into account not just the actions of the growth factors and receptors, but also the influence of soluble high affinity IGF binding proteins (IGFBPs).There is a recognition that IGFBPs exert IGF-dependent and IGF-independent effects in bone and other tissues and that an understanding of the mechanisms of action of IGFBPs and their regulation in the pericellular environment impact critically on tissue physiology. In this respect, a group of IGFBP proteinases (which may be considered as ancillary members of the IGF axis) play a crucial role in regulating IGFBP function. In this model, cleavage of IGFBPs by specific proteinases into fragments with lower affinity for growth factor(s) regulates the partition of IGFs between IGFBPs and cell surface IGF receptors. In this review, we examine the importance of IGFBP function in bone tissue with special emphasis on the role of pregnancy associated plasma protein-A (PAPP-A). We examine the function of PAPP-A primarily as an IGFBP-4 proteinase and present evidence that PAPP-A induced cleavage of IGFBP-4 is potentially a key regulatory step in bone metabolism. We also highlight some recent findings with regard to IGFBP-2 and IGFBP-5 (also PAPP-A substrates) function in bone tissue and briefly discuss the actions of the other three IGFBPs (-1, -3, and -6) in this tissue. Although our main focus will be in bone we will allude to IGFBP activity in other cells and tissues where appropriate.
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影响因子：
11.1
作者：
Argente J;Chowen JA;Pérez-Jurado LA;Frystyk J;Oxvig C
通讯作者：
Oxvig C
影响因子：
3.7
作者：
Christians JK;de Zwaan DR;Fung SH
通讯作者：
Fung SH
影响因子：
1.4
作者：
Amiri, Neilab;Christians, Julian K.
通讯作者：
Christians, Julian K.
DOI：
10.1152/ajpendo.2001.281.2.e283
发表时间：
2001-08-01
影响因子：
5.1
作者：
Andress, DL
通讯作者：
Andress, DL
影响因子：
11.5
作者：
Atzori, Francesco;Tabernero, Josep;Baselga, Jose
通讯作者：
Baselga, Jose