PKCβ Positively Regulates RANKL-Induced Osteoclastogenesis by Inactivating GSK-3β
| Autor: | Jihye Shin, Soo Young Lee, Jingjing Lin, Hyunduk Jang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
musculoskeletal diseases Cell signaling Indoles Osteoclasts Protein Kinase C beta Article glycogen synthase kinase-3β Maleimides Glycogen Synthase Kinase 3 Mice Osteoclast medicine Animals Bone Resorption Phosphorylation RNA Small Interfering Glycogen synthase Molecular Biology GSK3B Cells Cultured Protein kinase C osteoclast differentiation receptor activator of NF-κB ligand Glycogen Synthase Kinase 3 beta protein kinase Cβ NFATC Transcription Factors biology RANK Ligand Skull Cell Differentiation Cell Biology General Medicine Up-Regulation Mice Inbred C57BL medicine.anatomical_structure RANKL biology.protein Cancer research Signal Transduction |
| Zdroj: | Molecules and Cells |
| ISSN: | 0219-1032 1016-8478 |
| Popis: | 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-κB 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. |
| Databáze: | OpenAIRE |
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