Participation of protein kinase c β 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-βII was upregulated in differentiated cells. Reverse transcription–polymerase chain reaction and Western blotting analyses also showed an increase in PKC-βI as well as PKC-βII 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-κB ligand (RANKL). Use of an antisense oligonucleotide to PKC-βII resulted in a reduction in the RANKL-driven osteoclastogenesis. Pharmacological intervention with PKC-β activity by the specific inhibitor CG53353 suppressed cellular differentiation and fusion processes during osteoclastogenesis and inhibited bone-resorbing function of mature osteoclasts. PKC-β inhibition abolished the ERK and MEK activation by macrophage-colony stimulating factor and RANKL in osteoclast precursor cells whereas the cytokine-induced NF-κB activation was not hampered by the PKC-β inhibition. Our findings indicate that PKC-β has a role in regulation of osteoclast formation and function potentially by participating in the ERK signaling pathway of M-CSF and RANKL.