Inhibition of osteoclast differentiation and bone resorption by a novel lysophosphatidylcholine derivative, SCOH.
Osteoclasts are multinucleated cells formed by multiple steps of cell differentiation from progenitor cells of hematopoietic origin. Intervention in osteoclast differentiation is considered as an effective therapeutic approach to the treatment for bone diseases involving osteoclasts. In this study, we found that the organic compound (S)-1-lyso-2-stearoylamino-2-deoxy-sn-glycero-3-phosphatidylcholine (SCOH) inhibited osteoclast differentiation. The inhibitory effect of SCOH was observed in mouse bone marrow cell cultures supported either by coculturing with osteoblasts or by adding macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand (RANKL). M-CSF and RANKL activate the ERK, Akt, and NF-kappaB signal transduction pathways, and SCOH suppressed this activation. SCOH also inhibited the bone resorptive activity of differentiated osteoclasts. It attenuated bone resorption, actin ring formation, and survival of mature osteoclasts. Reduced activation of Akt and NF-kappaB and decreased induction of XIAP were observed in mature osteoclasts treated with SCOH. Thus, this novel phosphatidylcholine derivative may be useful for treating bone-resorption diseases.
Kwak
Han Bok
HB
Department of Chemistry, Division of Molecular Life Science, Ewha Womans University, Seoul 120-750, South Korea.
Lee
Soo Woong
SW
Li
Yin-Ji
YJ
Kim
Young-Ah
YA
Han
So-Yeop
SY
Jhon
Gil-Ja
GJ
Kim
Hong-Hee
HH
Lee
Zang Hee
ZH
D000199:Actins / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004347:Drug Interactions; D008244:Lysophosphatidylcholines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D015398:Signal Transduction; D051636:X-Linked Inhibitor of Apoptosis Protein
C483538:(S)-1-lyso-2-stearoylamino-2-deoxy-sn-glycero-3-phosphatidylcholine; D000199:Actins; D002352:Carrier Proteins; D008244:Lysophosphatidylcholines; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011506:Proteins; D011518:Proto-Oncogene Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D051636:X-Linked Inhibitor of Apoptosis Protein; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt