Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors

Signaling between osteoblasts and osteoclasts is important in bone homeostasis. We previously showed that human osteoblasts propagate intercellular calcium signals via two mechanisms: autocrine activation of P2Y receptors, and gap junctional communication. In the current work we identified mechanically induced intercellular calcium signaling between osteoblasts and osteoclasts and among osteoclasts. Intercellular calcium responses in osteoclasts required P2 receptor activation but not gap junctional communication. Pharmacological studies and reverse transcriptase-PCR amplification demonstrated that human osteoclasts expressed functional P2Y1 receptors, but, unexpectedly, desensitization of P2Y1 did not block calcium signaling to osteoclasts. We also found that osteoclasts expressed functional P2X7 receptors and showed that pharmacological inhibition of these receptors blocked calcium signaling to osteoclasts. Thus these studies show that calcium signaling between osteoblasts and osteoclasts occurs via activation of P2 receptors, but that different families of P2 receptors are required for calcium signaling in these two cell types. Intercellular calcium signaling among bone cells is therefore amenable to pharmacological manipulation that will specifically affect only bone-forming or bone-resorbing cells. P2 receptors may be important drug targets for the modulation of bone turnover.