Roles of Mitogen-Activated Protein Kinases in Osteoclast Biology.
Roles of Mitogen-Activated Protein Kinases in Osteoclast Biology.
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DOI：
10.3390/ijms19103004
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发表时间：
2018-10-01
影响因子：
5.6
通讯作者：
Jeong D
中科院分区：
文献类型：
--
作者：
Lee K;Seo I;Choi MH;Jeong D
骨经历了持续的重塑，这是由骨形成的成骨细胞和骨降解的破骨细胞之间的协调通讯稳态调节。多核巨型破骨细胞是唯一能够降解或吸收有机和无机骨成分的特化细胞。它们分泌蛋白酶（如组织蛋白酶K），降解有机胶原基质，并通过质子泵送在骨吸收部位建立局部酸中毒，以促进无机矿物的溶解。骨质疏松症是最常见的骨骼疾病，是由骨吸收过度引起的，这突出了破骨细胞在完整骨重塑中的关键作用。丝裂原活化蛋白激酶（MAPKs）介导的信号传导，包括细胞外信号调节激酶（ERK）、c-Jun n-末端激酶（JNK）和p38，已被认为是正常破骨细胞分化和激活的关键。各种外源性（如toll样受体激动剂）和内源性（如生长因子和炎症细胞因子）刺激有助于确定MAPKs是否正或负调节破骨细胞粘附、迁移、融合和存活以及破骨细胞骨吸收。在这篇综述中，我们描述了mapk在破骨细胞代谢中的独特作用，并概述了激活或抑制mapk及其下游靶点的上游调节因子。此外，我们还讨论了目前关于ERK、JNK和p38的差异动力学的知识，以及mapk在破骨细胞代谢中的串扰。
Bone undergoes continuous remodeling, which is homeostatically regulated by concerted communication between bone-forming osteoblasts and bone-degrading osteoclasts. Multinucleated giant osteoclasts are the only specialized cells that degrade or resorb the organic and inorganic bone components. They secrete proteases (e.g., cathepsin K) that degrade the organic collagenous matrix and establish localized acidosis at the bone-resorbing site through proton-pumping to facilitate the dissolution of inorganic mineral. Osteoporosis, the most common bone disease, is caused by excessive bone resorption, highlighting the crucial role of osteoclasts in intact bone remodeling. Signaling mediated by mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, has been recognized to be critical for normal osteoclast differentiation and activation. Various exogenous (e.g., toll-like receptor agonists) and endogenous (e.g., growth factors and inflammatory cytokines) stimuli contribute to determining whether MAPKs positively or negatively regulate osteoclast adhesion, migration, fusion and survival, and osteoclastic bone resorption. In this review, we delineate the unique roles of MAPKs in osteoclast metabolism and provide an overview of the upstream regulators that activate or inhibit MAPKs and their downstream targets. Furthermore, we discuss the current knowledge about the differential kinetics of ERK, JNK, and p38, and the crosstalk between MAPKs in osteoclast metabolism.
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影响因子：
4.6
作者：
Cong Q;Jia H;Li P;Qiu S;Yeh J;Wang Y;Zhang ZL;Ao J;Li B;Liu H
通讯作者：
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影响因子：
3.7
作者：
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影响因子：
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作者：
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Coetzee, Magdalena
DOI：
10.1097/01.asn.0000081663.52165.66
发表时间：
2003-09-01
影响因子：
13.6
作者：
Giachelli, CM
通讯作者：
Giachelli, CM
影响因子：
4
作者：
David, JP;Sabapathy, K;Wagner, EF
通讯作者：
Wagner, EF