YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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The Stimulatory Effect of P2Y6 Receptor Antagonist on RANKL-induced Osteoclastogenesis

P2Y6 수용체 길항제의 파골세포 분화 촉진 효과 규명

  • Received : 2015.05.07
  • Accepted : 2015.09.09
  • Published : 2015.10.31
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Abstract

P2Y receptors, a type of P2 receptor family, are G-protein coupled receptors and 8 subtypes have been characterized ($P2Y_1$, $P2Y_2$, $P2Y_4$, $P2Y_6$, $P2Y_{11-14}$). Recently, several studies have shed light on the role of P2Y receptors in bone biology. Among them, little is known on the role of $P2Y_6$ receptor on osteoclast differentiation. Thus, we investigated the role of $P2Y_6$ receptor on osteoclastogenesis using $P2Y_6$ receptor selective antagonist, MRS 2578. When osteoblasts and bone marrow cells were co-cultured in the presence of $VitD_3$ and $PGE_2$, $P2Y_6$ antagonist increased the formation of TRAP positive osteoclasts. To elucidate the target cells of $P2Y_6$ antagonist, we first checked the effect of MRS 2578 on osteoblasts. Treatment of MRS 2578 did not affect OPG : RANKL mRNA ratio in osteoblasts. Next, we checked the effects of $P2Y_6$ antagonist on osteoclast precursors using mouse bone marrow macrophages (BMMs). Addition of MRS 2578 increased the number of osteoclasts in RANKL-treated BMMs. Although $P2Y_6$ antagonist had no effect on RANKL-induced NFATc1, c-Fos and MafB expression levels, it significantly stimulated RANKL-induced Blimp1 mRNA expression in BMMs. Taken together, these data indicate that $P2Y_6$ antagonist increases osteoclast formation by upregulation of Blimp1 expression.

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References

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