Involvement of P2X4 receptor in osteoblast differentiation

Kito Hiroaki, Ryu Takusei, Saiga Noriaki, Endo Kyoko, Kajikuri Junko, Ohya Susumu

doi:10.1254/jpssuppl.97.0_3-b-p-002

<p>Osteoblast growth and differentiation, which are controlled by Ca²⁺ signaling, are important for bone formation and homeostasis. ATP released from hemichannels, such as pannexins and connexins located within the cell membrane, also contributes to osteoblast differentiation. The purpose of this study is to elucidate the functional relationship between hemichannel-mediated ATP efflux and P2X receptor in osteoblast differentiation of the osteoblastic cell line MC3T3-E1, established from mouse calvaria. </p><p>We found that the pharmacological blockade of hemichannels decreased the amount of released ATP from MC3T3-E1 cells during osteoblast differentiation. The expression levels of the alkaline phosphatase ALP, an osteoblast differentiation marker, were also suppressed by the treatment with CBX, a hemichannel blocker and 5-BDBD, a P2X4 blocker. ATP stimulation induced a transient Ca²⁺ influx through ATP-sensitive Ca²⁺ permeable channels, and this ATP-stimulated [Ca²⁺]_i rises were attenuated by the treatment with 5-BDBD. In addition, the endochondral ossification of metatarsal bones was inhibited by the treatment with CBX and 5-BDBD. These results suggest that ATP efflux via hemichannels may be involved in P2X4 mediated-ATP signaling during osteoblast differentiation. The functional coupling between hemichannels and P2X4 receptors plays an essential role in maintaining the bone homeostasis via modulating osteoblast differentiation.</p>

Involvement of P2X4 receptor in osteoblast differentiation

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