View : 27 Download: 0
PKC beta Positively Regulates RANKL-Induced Osteoclastogenesis by Inactivating GSK-3 beta
- PKC beta Positively Regulates RANKL-Induced Osteoclastogenesis by Inactivating GSK-3 beta
- Shin, Jihye; Jang, Hyunduk; Lin, Jingjing; Lee, Soo Young
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- MOLECULES AND CELLS
- 1016-8478; 0219-1032
- vol. 37, no. 10, pp. 747 - 752
- glycogen synthase kinase-3 beta; osteoclast differentiation; protein kinase C beta; receptor activator of NF-kappa B ligand
- KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
- SCI; SCIE; SCOPUS; KCI
- 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. expression is increased by RANKL. Pharmacological inhibition of PKC. 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. 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. 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.
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.