Serine/threonine phosphatases in osteoclastogenesis and bone resorption.

Serine/threonine phosphatases in osteoclastogenesis and bone resorption.
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丝氨酸/苏氨酸磷酸酶在破骨细胞形成和骨吸收中的作用。

DOI:
10.1016/j.gene.2020.145362
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发表时间:
2021-03-01
期刊:
影响因子:
3.5
通讯作者:
Bradley EW
Bradley EW
中科院分区:
生物学3区
文献类型:
--
作者:
Karkache IY;Damodaran JR;Molstad DHH;Bradley EW

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最佳骨量的维持是通过多种细胞类型(包括骨吸收破骨细胞)的协同功能来控制的。破骨细胞的作用是在发育骨建模过程中去除钙化组织,并在骨重塑过程中降解受损部位的骨。破骨细胞生成和/或分解代谢活动的改变可能会引起骨稳态的变化,但合成代谢活动不能抵消这种变化;因此,调节破骨细胞生成和骨吸收的因素对于进一步了解基础骨生物学以及作为治疗干预的潜在目标很有意义。包括 Rankl 和 M-csf 在内的几种关键细胞因子以及共刺激因子可引发促进破骨细胞生成的激酶信号级联反应。这些激酶级联被蛋白磷酸酶(包括丝氨酸/苏氨酸磷酸酶家族成员)的作用抵消。在这里,我们回顾了丝氨酸/苏氨酸磷酸酶的功能及其对破骨细胞分化和功能的控制,同时强调了我们对该领域内这一类未充分研究的蛋白质的理解的缺陷。
Maintenance of optimal bone mass is controlled through the concerted functions of several cell types, including bone resorbing osteoclasts. Osteoclasts function to remove calcified tissue during developmental bone modeling, and degrade bone at sites of damage during bone remodeling. Changes to bone homeostasis can arise with alterations in osteoclastogenesis and/or catabolic activity that are not offset by anabolic activity; thus, factors that regulate osteoclastogenesis and bone resorption are of interest to further our understanding of basic bone biology, and as potential targets for therapeutic intervention. Several key cytokines, including Rankl and M-csf, as well as co-stimulatory factors elicit kinase signaling cascades that promote osteoclastogenesis. These kinase cascades are offset by the action of protein phosphatases, including members of the serine/threonine phosphatase family. Here we review the functions of serine/threonine phosphatases and their control of osteoclast differentiation and function, while highlighting deficiencies in our understanding of this understudied class of proteins within the field.
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