Regulation of human osteoclast development by dendritic cell-specific transmembrane protein (DC-STAMP).
Regulation of human osteoclast development by dendritic cell-specific transmembrane protein (DC-STAMP).
复制标题
DOI：
10.1002/jbmr.531
复制
发表时间：
2012-01
影响因子：
6.2
通讯作者：
Ritchlin, Christopher T.
中科院分区：
文献类型：
--
作者：
Chiu, Ya-Hui;Mensah, Kofi A.;Schwarz, Edward M.;Ju, Yawen;Takahata, Masahiko;Feng, Changyong;McMahon, Loralee A.;Hicks, David G.;Panepento, Ben;Keng, Peter C.;Ritchlin, Christopher T.
破骨细胞（OC）是通过OC前体（OCP）融合产生的骨吸收多核细胞。OCP的发生率在糜烂性炎性关节炎和代谢性骨病患者中升高。虽然已知许多细胞因子和细胞表面受体参与破骨细胞生成，但对这种细胞转化调节的分子机制知之甚少。在此，我们集中我们的研究树突状细胞特异性跨膜蛋白（DC-STAMP），七次跨膜受体样蛋白已知是必不可少的细胞间融合破骨细胞。我们在DC-STAMP的胞质尾区鉴定了一个基于免疫受体酪氨酸的抑制基序（ITIM），并开发了一种抗DC-STAMP的单克隆抗体1A 2，该抗体检测了人肿瘤巨细胞上DC-STAMP的表达，在体外阻断了OC的形成，并区分了与OC电位呈正相关的四种人PBMC模式。在新鲜分离的单核细胞中，DC-STAMP高细胞在培养物中比DC-STAMP低细胞产生更高数量的OC，并且在破骨细胞生成期间DC-STAMP的表面表达逐渐下降。重要的是，我们发现DC-STAMP在其酪氨酸残基上被磷酸化，并分别与SHP-1和CD 16（一种含SH 2结构域的酪氨酸磷酸酶和一种ITAM相关蛋白）发生物理相互作用。总之，这些数据表明DC-STAMP是炎性关节炎中潜在的OCP生物标志物。此外，除了其对细胞融合的影响外，DC-STAMP还在破骨细胞生成期间动态调节细胞信号传导。
Osteoclasts (OC) are bone-resorbing, multinucleated cells that are generated via fusion of OC precursors (OCP). The frequency of OCP is elevated in patients with erosive inflammatory arthritis and metabolic bone diseases. Although many cytokines and cell surface receptors are known to participate in osteoclastogenesis, the molecular mechanisms underlying the regulation of this cellular transformation are poorly understood. Herein, we focused our studies on the dendritic cell-specific transmembrane protein (DC-STAMP), a seven-pass-transmembrane receptor-like protein known to be essential for cell-to-cell fusion during osteoclastogenesis. We identified an immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic tail of DC-STAMP, and developed an anti-DC-STAMP monoclonal antibody 1A2 that detected DC-STAMP expression on human tumor giant cells, blocked OC formation in vitro, and distinguished four patterns of human PBMC with a positive correlation to OC potential. In freshly isolated monocytes, DC-STAMPhigh cells produced a higher number of OC in culture than DC-STAMPlow cells and the surface expression of DC-STAMP gradually declined during osteoclastogenesis. Importantly, we showed that DC-STAMP is phosphorylated on its tyrosine residues and physically interacts with SHP-1 and CD16, an SH2-domain-containing tyrosine phosphatase and an ITAM-associated protein, respectively. Taken together, these data show that DC-STAMP is a potential OCP biomarker in inflammatory arthritis. Moreover, in addition to its effect on cell fusion, DC-STAMP dynamically regulates cell signaling during osteoclastogenesis.
登录
查看更多内容
影响因子：
4.9
作者：
Komano Y;Nanki T;Hayashida K;Taniguchi K;Miyasaka N
通讯作者：
Miyasaka N
影响因子：
4.1
作者：
Aoki, K;Didomenico, E;Baron, R
通讯作者：
Baron, R
影响因子：
4.4
作者：
Mori, Yu;Tsuji, Sukenao;Takai, Toshiyuki
通讯作者：
Takai, Toshiyuki
DOI：
10.1016/j.bbrc.2010.02.013
发表时间：
2010-03-12
影响因子：
3.1
作者：
Hayashi, Mikihito;Nakashima, Tomoki;Takayanagi, Hiroshi
通讯作者：
Takayanagi, Hiroshi
影响因子：
15.3
作者：
Kukita, T;Wada, N;Kukita, A;Kakimoto, T;Sandra, F;Toh, K;Nagata, K;Iijima, T;Horiuchi, M;Matsusaki, H;Hieshima, K;Yoshie, O;Nomiyama, H
通讯作者：
Nomiyama, H