MAGED1 Is a Negative Regulator of Bone Remodeling in Mice
MAGED1 Is a Negative Regulator of Bone Remodeling in Mice
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MAGED1 是小鼠骨重塑的负调节因子
DOI：
10.1016/j.ajpath.2015.06.017
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发表时间：
2015-10-01
影响因子：
6
通讯作者：
Wen, Chuanjun
中科院分区：
文献类型：
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作者：
Liu, Mei;Xu, Lijuan;Wen, Chuanjun
黑色素瘤抗原家族D1（MAGED 1）是一种重要的衔接蛋白，广泛表达并在细胞活动和生理功能的许多方面发挥重要作用。然而，其在骨重建中的作用仍然未知。因此，我们分析了Maged 1缺陷小鼠的骨表型。Magedi缺陷型小鼠表现出显著的骨密度降低和骨小梁结构恶化的骨质疏松表型。组织形态学分析表明，增加矿物质沉积率以及破骨细胞的数量和表面在Maged 1敲除小鼠。在细胞水平上，Magedi缺陷的成骨细胞表现出增加的增殖率和加速的分化。MAGED 1缺陷也引起破骨细胞生成的促进，这归因于破骨细胞中细胞自主加速分化和成骨细胞中NF-κ B配体/骨保护素比率的受体激活剂增加，这是破骨细胞生成的主要指标。因此，我们在小鼠模型中鉴定MAGED 1为成骨细胞生成、破骨细胞生成和骨重建的新型调节因子。
Melanoma antigen family D1 (MAGED1), an important adaptor protein, has been shown to ubiquitously express and play critical roles in many aspects of cellular events and physiological functions. However, its role in bone remodeling remains unknown. We, therefore, analyzed the bone phenotype of Maged1-deficient mice. Magedi-deficient mice displayed a significant osteoporotic phenotype with a marked decrease in bone density and deterioration of trabecular architecture. Histomorphometric analysis demonstrated an increased mineral apposition rate as well as increased osteoclast number and surface in Maged1 knockout mice. At the cellular level, Magedi-deficient osteoblasts exhibited an increased proliferation rate and accelerated differentiation. MAGED1 deficiency also caused a promotion in osteoclastogenesis, and that was attributed to the cell autonomous acceleration of differentiation in osteoclasts and an increased receptor activator of NF-kappa B Ligand/osteoprotegerin ratio, a major index of osteoclastogenesis, in osteoblasts. Thus, we identified MAGED1 as a novel regulator of osteoblastogenesis, osteoclastogenesis, and bone remodeling in a mouse model.