Conditional deletion of CD98hc inhibits osteoclast development.
Conditional deletion of CD98hc inhibits osteoclast development.
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DOI：
10.1016/j.bbrep.2015.11.023
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发表时间：
2016-03
影响因子：
2.7
通讯作者：
Ito Y
中科院分区：
文献类型：
--
作者：
Tsumura H;Ito M;Takami M;Arai M;Li XK;Hamatani T;Igarashi A;Takada S;Miyado K;Umezawa A;Ito Y
CD98重链（CD98hc）调节病毒诱导的细胞融合和单核细胞融合，并参与氨基酸运输。在这里，我们使用 CD98hcflox/floxLysM-cre 腹膜巨噬细胞（CD98hc 缺陷型巨噬细胞）检查了 CD98hc 在破骨细胞形成中所起的作用。在 1,25(OH)2 维生素 D3 存在下，与成骨细胞共培养，刺激腹膜巨噬细胞，然后用抗酒石酸盐酸性磷酸酶染色液染色。与野生型小鼠相比，CD98hc 缺陷小鼠腹腔巨噬细胞的多核破骨细胞形成严重受损。 CD98hc 通过 CD98 轻链 (CD98lc) 介导整合素信号传导和氨基酸转运。在整合素信号传导中，在 CD98h 缺陷腹膜巨噬细胞的触发期观察到 M-CSF-RANKL 诱导的 ERK、Akt、JNK 和 p130Cas 磷酸化受到抑制。此外，我们发现，由氨基酸饥饿激活的一般控制非阻抑（GCN）途径是由 RANKL 刺激的 CD98hc 缺陷腹膜巨噬细胞诱导的。这些结果表明CD98通过整合素信号传导和氨基酸转运在破骨细胞形成中发挥两个重要作用。 CD98hc 缺陷型巨噬细胞的破骨细胞生成严重受损。 CD98hc 缺陷的腹膜巨噬细胞陷入氨基酸饥饿，导致破骨细胞生成中诱导通用控制非阻抑 (GCN) 途径。
The CD98 heavy chain (CD98hc) regulates virus-induced cell fusion and monocyte fusion, and is involved in amino acid transportation. Here, we examined the role that CD98hc plays in the formation of osteoclasts using CD98hcflox/floxLysM-cre peritoneal macrophages (CD98hc-defect macrophages). Peritoneal macrophages were stimulated with co-cultured with osteoblasts in the presence of 1,25(OH)2 vitamin D3, and thereafter stained with tartrate-resistant acid phosphatase staining solution. The multinucleated osteoclast formation was severely impaired in the peritoneal macrophages isolated from the CD98hc-defect mice compared with those from wild-type mice. CD98hc mediates integrin signaling and amino acid transport through the CD98 light chain (CD98lc). In integrin signaling, suppression of the M-CSF-RANKL-induced phosphorylation of ERK, Akt, JNK and p130Cas were observed at the triggering phase in the CD98h-defect peritoneal macrophages. Moreover, we showed that the general control non-derepressible (GCN) pathway, which was activated by amino acid starvation, was induced by the CD98hc-defect peritoneal macrophages stimulated with RANKL. These results indicate that CD98 plays two important roles in osteoclast formation through integrin signaling and amino acid transport. The osteoclastogenesis was severely impaired in the CD98hc-defect macrophages. CD98hc-defect peritoneal macrophages fall into amino acid starvation, resulting in inducing the general control non-derepressible (GCN) pathway in the osteoclastogenesis.