A hybrid peptide derived from cecropin-A and magainin-2 inhibits osteoclast differentiation.
The adult skeleton is in a dynamic state, being continually broken down and reformed by the coordinated actions of osteoclasts and osteoblasts. Increased osteoclast activity may contribute to the development of osteoporosis. Therefore, the intervention of osteoclast-mediated bone resorption is considered as an effective therapeutic approach in the treatment of osteoporosis. In the course of searching for agents that inhibit osteoclast differentiation and activation, we found that a novel hybrid peptide P1 derived from cecropin-A and magainin-2 reduced osteoclast differentiation in various osteoclast culture systems. As this peptide had no cytotoxicity on various cultures of primary cells and established cell lines, its inhibitory effect on osteoclastogenesis was not due to general cytotoxicity. The effects of P1 on osteoclasts appear to be mediated through the inhibition of NF-kappaB and JNK activation induced by the osteoclastogenic cytokine, receptor activator of NF-kappaB ligand (RANKL). These results provide an evidence for the potential usefulness of P1 for the treatment of bone-resorbing diseases.
Kwak
Han Bok
HB
National Research Laboratory for Bone Metabolism, Chosun University, Gwangju, South Korea.
Lee
Soo Woong
SW
Lee
Dong Gun
DG
Hahm
Kyung Soo
KS
Kim
Kyung Keun
KK
Kim
Hong-Hee
HH
Lee
Zang Hee
ZH
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D001862:Bone Resorption / Q000139:chemically induced / Q000473:pathology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D004285:Dogs; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D017737:Macrophages, Peritoneal / Q000187:drug effects; D054806:Magainins; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D016328:NF-kappa B / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects*; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013234:Stem Cells; D029867:Xenopus Proteins
D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054806:Magainins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010455:Peptides; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; C031161:cecropin A; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases