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Updated: Apr 23, 2026

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
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A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

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

Jihye Shin1, Hyunduk Jang2, Jingjing Lin1

  • 1Department of Life Science and the Research Center for Cellular Home-ostasis, Ewha Womans University, Seoul 120-750, Korea.

Molecules and Cells
|September 27, 2014
PubMed

Insights

Protein Kinase C beta (PKCβ) promotes osteoclast formation by inactivating GSK-3β and boosting NFATc1. Inhibiting PKCβ reduces bone destruction, offering therapeutic potential for inflammatory bone diseases.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Bone Biology

Background:

  • Protein kinase C (PKC) family members are crucial in cellular signaling, phosphorylating diverse targets.
  • The specific role of PKC in receptor activator of NF-κB ligand (RANKL) signaling remained unclear.
  • Osteoclastogenesis, the formation of bone-resorbing cells, is a key process in bone remodeling and disease.

Purpose of the Study:

  • To elucidate the role of PKC in RANKL-induced osteoclastogenesis.
  • To investigate the specific PKC isoforms involved in this pathway.
  • To assess the therapeutic potential of targeting PKC in bone destruction.

Main Methods:

  • Examined PKC isoform expression in response to RANKL.
  • Utilized pharmacological inhibitors and RNA interference to modulate PKCβ activity.
  • Assessed osteoclast formation, NFATc1 induction, and GSK-3β phosphorylation.
  • Evaluated the effect of PKC inhibition on RANKL-induced bone destruction in vivo.

Main Results:

  • RANKL stimulation increases PKCβ expression.
  • PKCβ inhibition or down-regulation suppresses osteoclast differentiation and NFATc1 induction.
  • PKCβ inactivation of GSK-3β is critical for NFATc1 induction.
  • PKCβ inhibition protects against RANKL-induced bone destruction in mice.

Conclusions:

  • PKCβ acts as a positive regulator in RANKL-induced osteoclastogenesis by inactivating GSK-3β and promoting NFATc1 induction.
  • The PKCβ pathway is essential for osteoclast differentiation.
  • Targeting PKCβ offers a promising therapeutic strategy for inflammatory bone diseases characterized by excessive bone resorption.
Keywords:
glycogen synthase kinase-3βosteoclast differentiationprotein kinase Cβreceptor activator of NF-κB ligand

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