Participation of protein kinase C beta in osteoclast differentiation and function.
Protein kinase C (PKC) proteins have been shown to be involved in diverse cellular responses of various cell types. In experiments to identify genes regulated during osteoclast differentiation by a cDNA microarray approach, we found that the gene expression of PKC-betaII was upregulated in differentiated cells. Reverse transcription-polymerase chain reaction and Western blotting analyses also showed an increase in PKC-betaI as well as PKC-betaII during osteoclast formation in mouse bone marrow cell cultures in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kappaB ligand (RANKL). Use of an antisense oligonucleotide to PKC-betaII resulted in a reduction in the RANKL-driven osteoclastogenesis. Pharmacological intervention with PKC-beta activity by the specific inhibitor CG53353 suppressed cellular differentiation and fusion processes during osteoclastogenesis and inhibited bone-resorbing function of mature osteoclasts. PKC-beta inhibition abolished the ERK and MEK activation by macrophage-colony stimulating factor and RANKL in osteoclast precursor cells whereas the cytokine-induced NF-kappaB activation was not hampered by the PKC-beta inhibition. Our findings indicate that PKC-beta has a role in regulation of osteoclast formation and function potentially by participating in the ERK signaling pathway of M-CSF and RANKL.
Lee
S W
SW
National Research Laboratory for Bone Metabolism, Chosun University, Gwangju 501-759, South Korea.
Kwak
H B
HB
Chung
W J
WJ
Cheong
H
H
Kim
H-H
HH
Lee
Z H
ZH
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D064546:Protein Kinase C beta; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D020928:Mitogen-Activated Protein Kinases