Inhibition of osteoclast differentiation and bone resorption by a novel lysophosphatidylcholine derivative, SCOH.
Biochem Pharmacol
; 67(7): 1239-48, 2004 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-15013839
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
/
Lisofosfatidilcolinas
/
Diferenciação Celular
/
Proteínas Serina-Treonina Quinases
Limite:
Animals
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Coréia do Sul