Mex3B inhibits DC-STAMP mRNA level and osteoclastogenesis.
Mex3B inhibits DC-STAMP mRNA level and osteoclastogenesis.
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DOI：
10.1016/j.cellin.2021.100002
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发表时间：
2022-02
期刊：
影响因子：
--
通讯作者：
Wu, Huang-Ning
中科院分区：
文献类型：
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作者：
Yang, Yan;Wang, Su-Yun;Li, Zhen-Qi;Wu, Huang-Ning
通过破骨细胞驱动的骨吸收和成骨细胞介导的骨形成的持续重塑来维持骨稳态。破骨细胞是从单核细胞谱系的髓样祖细胞分化而来的多核巨细胞（MNCs）。在破骨细胞成熟过程中，DC-STAMP（树突状细胞特异性跨膜蛋白）已被证明是破骨细胞融合的主要决定因素。在这项研究中，我们证明，Mex 3B抑制破骨细胞融合蛋白DCSTAMP的表达和破骨细胞的生成。在破骨细胞的分化过程中，Mex 3B的表达被细胞因子如RANKL和TNFa下调，导致Mex 3B介导的DC-STAMP mRNA水平的下调减轻。我们的研究结果不仅揭示了DC-STAMP介导的破骨细胞生成调控的关键机制，而且还指出Mex 3B作为治疗人类骨骼疾病的潜在治疗靶点。
Bone homeostasis is maintained through continuous remodeling by osteoclast-driven bone resorption and osteoblast-mediated bone formation. Osteoclasts are multinucleated giant cells (MNCs) differentiated from myeloid progenitors of the monocytic lineage. During osteoclast maturation, DC-STAMP (dendritic cell specific transmembrane protein) has been shown as a master determinant of osteoclast cell fusion. In this study, we demonstrate that Mex3B inhibits osteoclast fusion protein DCSTAMP expression and osteoclastogenesis. During differentiation of osteoclasts, the expression of Mex3B is down-regulated by cytokines such as RANKL and TNFa, resulting in relief of Mex3B-mediated down-regulation of DC-STAMP mRNA level. Our findings not only reveal critical mechanisms on regulation of DC-STAMP-mediated osteoclastogenesis, but also point to Mex3B as a potential therapeutic target for the treatment of human bone diseases.