CXC chemokine ligand 2 induced by receptor activator of NF-kappa B ligand enhances osteoclastogenesis.
CXCL2 has been known to regulate immune functions mainly by chemo-attracting neutrophils. In this study, we show that CXCL2 can be induced by receptor activator of NF-kappaB ligand, the osteoclast (OC) differentiation factor, through JNK and NF-kappaB signaling pathways in OC precursor cells. CXCL2 in turn enhanced the proliferation of OC precursor cells of bone marrow-derived macrophages (BMMs) through the activation of ERK. Knockdown of CXCL2 inhibited both the proliferation of and the ERK activation in BMMs. During osteoclastogenesis CXCL2 stimulated the adhesion and the migration of BMMs. Moreover, the formation of OCs from BMMs was significantly increased on treatment with CXCL2. Conversely, the CXCL2 antagonist repertaxin and a CXCL2 neutralizing Ab potently reduced receptor activator of NF-kappaB ligand-induced osteoclastogenesis. Furthermore, CXCL2 evoked fulminant bone erosion in the in vivo mouse experiments. Finally, prominent upregulation of CXCL2 was detected in synovial fluids and sera from rheumatoid arthritis patients, suggesting a potential involvement of CXCL2-mediated osteoclastogenesis in rheumatoid arthritis-associated bone destruction. Thus, CXCL2 is a novel therapeutic target for inflammatory bone destructive diseases.
Ha
Jeongim
J
Department of Cell and Developmental Biology, BK21 and DRI, Seoul National University School of Dentistry, Seoul, Korea.
Choi
Hyo-Sun
HS
Lee
Youngkyun
Y
Kwon
Hyung-Joo
HJ
Song
Yeong Wook
YW
Kim
Hong-Hee
HH
D000818:Animals; D001862:Bone Resorption / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000096:biosynthesis* / Q000172:deficiency / Q000502:physiology; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D053245:RANK Ligand / Q000502:physiology*; D013234:Stem Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D053245:RANK Ligand