Dok-1 and Dok-2 deficiency induces osteopenia via regulation of osteoclasts
Dok-1 and Dok-2 deficiency induces osteopenia via regulation of osteoclasts
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Dok-1 和 Dok-2 缺乏通过调节破骨细胞诱导骨质减少
DOI：
10.1002/jcp.22909
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Aya Kawamata
中科院分区：
文献类型：
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作者：
吉岡美紗子;石丸喜朗;朝倉富子;阿部啓子;長尾遥奈，西村伸一，藤澤和謙，珠玖隆行;Aya Kawamata
骨质疏松症导致骨折，导致生活质量下降，它是最普遍的疾病之一，它影响了大约10%的人口。骨质疏松症的一个重要特征是骨质减少。然而，其病因尚不完全清楚。Dok‐1和Dok‐2是作用于蛋白酪氨酸激酶下游的衔接蛋白，主要在造血细胞中表达。虽然这些蛋白对免疫系统有负调控作用，但它们在骨代谢中的作用尚不清楚。在这里，我们分析了Dok‐1和Dok‐2双缺乏对骨骼的影响。与野生型相比，Dok‐1/2缺乏降低了骨小梁和皮质骨量的水平。此外，Dok‐1/2缺乏增加了长骨中轴的骨膜周长和骨膜内周长。骨参数的组织形态学分析表明，Dok‐1/2缺乏没有显著改变骨形成参数的水平，包括矿化表面/骨表面（MS/BS）、矿物质附着率（MAR）和骨形成率（BFR）。相反，Dok‐1/2缺乏可提高骨吸收参数水平，包括破骨细胞数量（N.Oc/BS）和破骨细胞表面（Oc.S/BS）。个体破骨细胞活性分析表明，Dok‐1/2缺乏增强了小坑的形成。在系统上，Dok‐1/2缺乏增加了尿脱氧吡啶啉（Dpyr）的水平。寻找Dok‐1/2缺乏对破骨细胞影响的靶点发现，该突变增强了破骨细胞前体对巨噬细胞集落刺激因子的敏感性。这些数据表明，Dok‐1和Dok‐2缺乏通过激活破骨细胞诱导骨质减少。j .细胞。中国生物医学工程学报，2011,31(2):387 - 393。©2011 Wiley期刊公司
Osteoporosis causes fractures that lead to reduction in the quality of life and it is one of the most prevalent diseases as it affects approximately 10% of the population. One of the important features of osteoporosis is osteopenia. However, its etiology is not fully elucidated. Dok‐1 and Dok‐2 are adaptor proteins acting downstream of protein tyrosine kinases that are mainly expressed in the cells of hematopoietic lineage. Although these proteins negatively regulate immune system, their roles in bone metabolism are not understood. Here, we analyzed the effects of Dok‐1 and Dok‐2 double‐deficiency on bone. Dok‐1/2 deficiency reduced the levels of trabecular and cortical bone mass compared to wildtype. In addition, Dok‐1/2 deficiency increased periosteal perimeters and endosteal perimeters of the mid shaft of long bones. Histomorphometric analysis of the bone parameters indicated that Dok‐1/2 deficiency did not significantly alter the levels of bone formation parameters including mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR) and bone formation rate (BFR). In contrast, Dok‐1/2 deficiency enhanced the levels of bone resorption parameters including osteoclast number (N.Oc/BS) and osteoclast surface (Oc.S/BS). Analyses of individual osteoclastic activity indicated that Dok‐1/2 deficiency enhanced pit formation. Systemically, Dok‐1/2 deficiency increased the levels of urinary deoxypyridinoline (Dpyr). Search for the target point of the Dok‐1/2 deficiency effects on osteoclasts identified that the mutation enhanced sensitivity of osteoclast precursors to macrophage colony‐stimulating factor. These data revealed that Dok‐1 and Dok‐2 deficiency induces osteopenia by activation of osteoclasts. J. Cell. Physiol. 226: 3087–3093, 2011. © 2011 Wiley Periodicals, Inc.