Optineurin regulates osteoblastogenesis through STAT1
Optineurin regulates osteoblastogenesis through STAT1
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视神经磷酸酶通过STAT1调节成骨细胞的形成
DOI：
10.1016/j.bbrc.2020.03.028
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发表时间：
2020-05-14
影响因子：
3.1
通讯作者：
Kurihara, Hidemi
中科院分区：
文献类型：
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作者：
Mizuno, Noriyoshi;Iwata, Tomoyuki;Kurihara, Hidemi
破骨细胞的骨吸收与成骨细胞的骨形成之间复杂而微妙的平衡调节骨代谢。视神经磷酸酶（OPTN）是一种与原发性开角型青光眼和肌萎缩侧索硬化症有关的基因。虽然其功能已在眼科和神经病学中被广泛研究，但最近的报道显示其可能通过负调节破骨细胞分化而参与骨代谢。然而，关于OPTN在成骨细胞功能中的作用知之甚少。在这里，我们证明了OPTN不仅控制破骨细胞，而且还控制成骨细胞分化。在Optn（-/-）小鼠中评估了成骨细胞生成和破骨细胞生成中涉及的不同参数。结果表明，Optn（-/-）小鼠的成骨细胞碱性磷酸酶活性受损，矿化结节缺陷，不能支持破骨细胞分化。OPTN还可与成骨细胞中的信号转导和转录激活因子1（STAT 1）结合，通过调节STAT 1的表达水平来调节RUNX 2的核定位。这些数据表明，OPTN不仅通过调节破骨细胞功能，而且通过经由STAT 1介导RUNX 2核转位来调节成骨细胞功能而参与骨代谢。(C)2020爱思唯尔公司All rights reserved.
A sophisticated and delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts regulates bone metabolism. Optineurin (OPTN) is a gene involved in primary open-angle glaucoma and amyotrophic lateral sclerosis. Although its function has been widely studied in ophthalmology and neurology, recent reports have shown its possible involvement in bone metabolism through negative regulation of osteoclast differentiation. However, little is known about the role of OPTN in osteoblast function. Here, we demonstrated that OPTN controls not only osteoclast but also osteoblast differentiation. Different parameters involved in osteoblastogenesis and osteoclastogenesis were assessed in Optn(-/-) mice. The results showed that osteoblasts from Optn(-/-) mice had impaired alkaline phosphatase activity, defective mineralized nodules, and inability to support osteoclast differentiation. Moreover, OPTN could bind to signal transducer and activator of transcription 1 (STAT1) and regulate runt-related transcription factor 2 (RUNX2) nuclear localization by modulating STAT1 levels in osteoblasts. These data suggest that OPTN is involved in bone metabolism not only by regulating osteoclast function but also by regulating osteoblast function by mediating RUNX2 nuclear translocation via STAT1. (C) 2020 Elsevier Inc. All rights reserved.