PKCβ positively regulates RANKL-induced osteoclastogenesis by inactivating GSK-3β

Jihye Shin, Hyunduk Jang, Jingjing Lin, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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-kB ligand (RANKL) signaling has remained elusive. We now demonstrate that PKCβ acts as a positive regulator which inactivates glycogen synthase kinase-3β (GSK-3β) and promotes NFATc1 induction during RANKL-induced osteoclastogenesis. Among PKCs, PKCβ expression is increased by RANKL. Pharmacological inhibition of PKCβ decreased the formation of osteoclasts which was caused by the inhibition of NFATc1 induction. Importantly, the phosphorylation of GSK-3β was decreased by PKCβ inhibition. Likewise, down-regulation of PKCβ by RNA interference suppressed osteoclast differentiation, NFATc1 induction, and GSK-3β phosphorylation. The administration of PKC inhibitor to the RANKL-injected mouse calvaria efficiently protected RANKL-induced bone destruction. Thus, the PKCβ pathway, leading to GSK-3β inactivation and NFATc1 induction, has a key role in the differentiation of osteoclasts. Our results also provide a further rationale for PKCβ’s therapeutic targeting to treat inflammation-related bone diseases.

Original languageEnglish
Pages (from-to)747-752
Number of pages6
JournalMolecules and Cells
Issue number10
StatePublished - 2014

Bibliographical note

Publisher Copyright:
© The Korean Society for Molecular and Cellular Biology.


  • Glycogen synthase kinase-3β
  • Osteoclast differentiation
  • Protein kinase Cβ
  • Receptor activator of NF-kB ligand


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