Expression and possible role of PVR/CD155/Necl-5 in osteoclastogenesis |
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Authors: | Saori Kakehi Ken-ichi Nakahama Ikuo Morita |
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Institution: | (1) Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan;(2) 21st Century Center of Excellence (COE) Program for Molecular Destruction and Reconstitution of Tooth and Bone, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan |
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Abstract: | 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-1 negatively regulates osteoclast formation. Furthermore, our results indicate that
the cellular fusion process may be inhibited by the PVR-mediated signaling. |
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Keywords: | Poliovirus receptor DNAX accessory molecule-1 Osteoclastogenesis Cell fusion |
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