Expression and possible role of PVR/CD155/Necl-5 in osteoclastogenesis
Expression and possible role of PVR/CD155/Necl-5 in osteoclastogenesis
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DOI：
10.1007/s11010-007-9413-x
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发表时间：
2007-07-01
影响因子：
4.3
通讯作者：
Morita, Ikuo
中科院分区：
文献类型：
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作者：
Kakehi, Saori;Nakahama, Ken-ichi;Morita, Ikuo
破骨细胞是骨吸收细胞，通过两步细胞-细胞相互作用从造血祖细胞分化而来。一种是破骨细胞前体和基质细胞之间的相互作用，以启动分化。另一种是破骨细胞前体相互作用形成多核破骨细胞。近年来，脊髓灰质炎病毒受体(PVR、CD155、NECL-5)在细胞黏附和迁移中发挥重要作用。然而，PVR在破骨细胞形成中的作用尚未见报道。在本文中，我们检测了PVR及其配体DNAX辅助分子-1(dNaM-1，CD226)在破骨细胞前体、成熟破骨细胞和基质细胞中的表达。我们发现PVR在破骨细胞和基质细胞中都有结构性表达。在破骨细胞形成的不同阶段，PVR的表达没有变化。相反，dNaM-1在单个核细胞中表达，并在破骨细胞形成过程中下调。此外，作为PVR的可溶性配体的dNaM-1胞外区(ED-dNaM-1)可抑制多核破骨细胞的形成，但不影响单核前破骨细胞的形成。尤其是在培养7天时，ED-dNaM-1可抑制破骨细胞的形成，在第6天和第7天，单核前破骨细胞融合成多核破骨细胞。这种抑制作用可被针对PVR的小干扰RNA部分消除。这些结果表明，至少在一定程度上，PVR与dNaM-I的结合负向调节破骨细胞的形成。此外，我们的结果表明，PVR介导的信号转导可能会抑制细胞融合过程。
Osteoclasts, the bone-resorbing cells, are differentiated from hematopoietic precursors via two-step cell-cell interactions. One is the interaction between the osteoclast precursor and the stromal cell to initiate differentiation. The other is the interaction among osteoclast precursors to form multinucleated osteoclasts. Recently, the poliovirus receptor (PVR, CD155, Necl-5) was reported to play important roles in cell adhesion and migration. However, there are no reports of PVR in osteoclastogenesis. In this paper, we examined the expression of PVR and its ligand, DNAX accessory molecule-1 (DNAM-1, CD226), in osteoclast precursors, mature osteoclasts, and stromal cells. We found that the PVR was constitutively expressed in both osteoclast cells and stromal cells. The expression of PVR was not changed at various stages of osteoclast formation. In contrast, the expression of DNAM-1 was observed in mononuclear cells and was down-regulated during osteoclastogenesis. Moreover, multinucleated osteoclast formation was inhibited by treatment with the extracellular domain of DNAM-1 (ED-DNAM-1) as a soluble ligand for PVR, but mononuclear preosteoclast formation was not affected. Especially, during the 7-day cultivation, osteoclast formation was suppressed by the treatment with ED-DNAM-1 on days 6 and 7, when the mononuclear preosteoclasts fused into multinucleated osteoclasts. This suppression was abrogated partially by a small interfering RNA specific for PVR. These results suggest that, at least in part, the binding of PVR with DNAM-I negatively regulates osteoclast formation. Furthermore, our results indicate that the cellular fusion process may be inhibited by the PVR-mediated signaling.