Selective induction of P2Y14 receptor by RANKL promotes osteoclast formation.
The purinergic receptor P2Y, G protein coupled, 14 (P2Y14) receptor for UDP-glucose and other UDP-sugars has been implicated in the regulation of the stem cell compartment as well as neuroimmune function. However, the role of P2Y14 in osteoclast formation is completely unknown. We found that RANKL selectively induced P2Y14 among seven mammalian P2Y receptors when analysed at both the mRNA and protein level, but inhibitors of the mitogenactivated protein (MAP) kinase pathway suppressed induction of P2Y14 proteins. Extracellular addition of UDP-sugars such as UDP-glucose, UDP-galactose, UDP-glucuronic acid, and UDP-N-acetyl glucosamine promoted RANKL-induced osteoclastogenesis, while P2Y14 downregulation by RNA interference inhibited osteoclast formation. Taken together, these results suggest that P2Y14 may act as the receptor for UDP-sugars in osteoclast precusors and may regulate RANKL-induced osteoclastogenesis.
Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, 120-750, Korea.
Seung Ah
SA
Lee
Jin Hee
JH
Park
Soo Young
SY
Lee
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010024:Osteoporosis / Q000188:drug therapy; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000378:metabolism*; D058470:Receptors, Purinergic P2Y / Q000235:genetics / Q000378:metabolism
C509795:P2ry14 protein, mouse; D058912:Purinergic P2Y Receptor Agonists; D053245:RANK Ligand; D018048:Receptors, Purinergic P2; D058470:Receptors, Purinergic P2Y; C505689:Tnfsf11 protein, mouse