Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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PKCβ Positively Regulates RANKL-Induced Osteoclastogenesis by Inactivating GSK-3β

  • Shin, Jihye (Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Jang, Hyunduk (Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Lin, Jingjing (Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Lee, Soo Young (Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University)
  • Received : 2014.07.31
  • Accepted : 2014.08.18
  • Published : 2014.10.31
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Abstract

Protein kinase C (PKC) family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. However, the role of PKC in receptor activator of NF-${\kappa}B$ ligand (RANKL) signaling has remained elusive. We now demonstrate that $PKC{\beta}$ acts as a positive regulator which inactivates glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and promotes NFATc1 induction during RANKL-induced osteoclastogenesis. Among PKCs, $PKC{\beta}$ expression is increased by RANKL. Pharmacological inhibition of $PKC{\beta}$ decreased the formation of osteoclasts which was caused by the inhibition of NFATc1 induction. Importantly, the phosphorylation of GSK-$3{\beta}$ was decreased by $PKC{\beta}$ inhibition. Likewise, down-regulation of $PKC{\beta}$ by RNA interference suppressed osteoclast differentiation, NFATc1 induction, and GSK-$3{\beta}$ phosphorylation. The administration of PKC inhibitor to the RANKL-injected mouse calvaria efficiently protected RANKL-induced bone destruction. Thus, the $PKC{\beta}$ pathway, leading to GSK-$3{\beta}$ inactivation and NFATc1 induction, has a key role in the differentiation of osteoclasts. Our results also provide a further rationale for $PKC{\beta}$'s therapeutic targeting to treat inflammation-related bone diseases.

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References

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