Profiling signalling pathways of the receptor activator of NF-kappaB ligand-induced osteoclast formation in mouse monocyte cells, RAW264.7.
Cell-based signal chemical genomics can profile the signalling pathway for certain cellular events by using a target-known chemical library. To ascertain its usefulness, the receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis in mouse monocyte/macrophage cells RAW264.7 was used as an in vitro experimental model. Of 180 target-known inhibitors/activators formatted in a 384-well plate, 8 chemicals were shown to inhibit the osteoclast formation, but 4 chemicals enhanced this process. A variety of references support, or possibly lead one to expect the effects of these 12 chemicals on the cellular process of osteoclastogenesis in RAW264.7 cells, but several signalling pathways were newly found in this study; for example, CA-074 Me inhibiting cathepsin B and nitrendipine blocking the calcium channel could have the potential to inhibit the osteoclast formation as well as bone resorption. This is a simple but very fast and powerful method of profiling the signalling pathway of certain cellular events. Signal chemical genomics could provide invaluable information for the exploration of new target signalling processes and further target-based drug discovery strategies.
Kim
M H
MH
Department of Biochemistry, Chungnam National University, Daejeon, Korea.
Kim
B T
BT
Min
Y K
YK
Kim
S H
SH
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D007527:Isoenzymes / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction; D000071681:Tartrate-Resistant Acid Phosphatase
D007527:Isoenzymes; D008024:Ligands; D016328:NF-kappa B; D053245:RANK Ligand; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase