The blocking of uPAR suppresses lipopolysaccharide-induced inflammatory osteoclastogenesis and the resultant bone loss through attenuation of integrin ß3/Akt pathway.
Immun Inflamm Dis
; 4(3): 338-49, 2016 Sep.
Article
en En
| MEDLINE
| ID: mdl-27621816
INTRODUCTION: Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis, cause the bone destruction by promotion of the differentiation of monocyte/macrophage lineage cells into mature osteoclasts (OCs) with active bone-resorbing character. However, the detailed mechanisms underlying this disorder remain unclear. We herein investigated the role of urokinase plasminogen activator receptor (uPAR) in the bone destruction caused by chronic inflammation. METHODS: We investigated that the effect of uPAR on inflammatory OC formation induced by lipopolysaccharide (LPS) in inflammatory diseases. RESULTS: We found that the LPS more weakly induced OC formation and the resultant bone loss in uPAR-deficient mice than in wild-type mice. Additionally, we demonstrated that uPAR significantly potentiated LPS-induced OC formation of RAW264.7 mouse monocyte/macrophage linage cells in integrin ß3/Akt-dependent manner. Moreover, we showed that the blocking of uPAR function by the administration of anti-uPAR neutralizing antibody significantly attenuated the LPS-induced OC formation and the resultant bone loss in mice. CONCLUSIONS: These results strongly suggest that uPAR negatively regulates the LPS-induced inflammatory OC formation and the resultant bone loss mediated through the integrin ß3/Akt pathway. Our findings partly clarify the molecular mechanisms underlying bone destruction caused by chronic inflammatory diseases, and would benefit research on identifying antibody therapy for the treatment of these diseases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Immun Inflamm Dis
Año:
2016
Tipo del documento:
Article
Pais de publicación:
Reino Unido