LAUSR

Purinergic signaling plays important roles in bone. P2X5, a member of ligand‐gated ion channel receptors, has been demonstrated to regulate osteoclast maturation. However, the molecular mechanism of P2X5‐mediated osteoclast regulation remains unclear. Here, we identified methylosome protein 50 (MEP50), a critical cofactor of the protein arginine methyltransferase 5 (PRMT5), as a P2X5‐associating molecule. RNAi‐mediated knockdown of MEP50 results in decreased formation of mature osteoclasts. MEP50 associates with P2X5, and this association requires the C‐terminal intracellular region of P2X5. Additionally, impaired maturation of P2X5‐deficient osteoclasts could be restored by transduction of full‐length P2X5, but not a C‐terminal deletion mutant of P2X5. These results indicate that P2X5 associates with MEP50 and suggest a link between the PRMT5 complex and P2X5 signaling in osteoclast maturation.