RRC ID 63925
Author Lu DZ, Dong W, Feng XJ, Chen H, Liu JJ, Wang H, Zang LY, Qi MC.
Title CaMKII(δ) regulates osteoclastogenesis through ERK, JNK, and p38 MAPKs and CREB signalling pathway.
Journal Mol Cell Endocrinol
Abstract Calcium/calmodulin-dependent protein kinases (CaMKs) are a group of important molecules mediating calcium signal transmission and have been proved to participate in osteoclastogenesis regulation. CaMKII, a subtype of CaMKs is expressed during osteoclast differentiation, but its role in osteoclastogenesis regulation remains controversial. In the present study, we identified that both mRNA and protein levels of CaMKII (δ) were upregulated in a time-dependent manner during osteoclast differentiation. CaMKII (δ) gene silencing significantly inhibited osteoclast formation, bone resorption, and expression of osteoclast-related genes, including nuclear factor of activated T cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and c-Src. Furthermore, CaMKII (δ) gene silencing downregulated phosphorylation of mitogen-activated protein kinases (MAPKs), including JNK, ERK, and p38, which were transiently activated by RANKL. Specific inhibitors of ERK, JNK, and p38 also markedly inhibited expression of osteoclast-related genes, osteoclast formation, and bone resorption like CaMKII (δ) gene silencing. Additionally, CaMKII (δ) gene silencing also suppressed RANKL-triggered CREB phosphorylation. Collectively, these data demonstrate the important role of CaMKII (δ) in osteoclastogenesis regulation through JNK, ERK, and p38 MAPKs and CREB pathway.
Volume 508
Pages 110791
Published 2020-5-15
DOI 10.1016/j.mce.2020.110791
PII S0303-7207(20)30091-5
PMID 32173349
MeSH Animals Bone Resorption / genetics Bone Resorption / pathology Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism* Cell Differentiation / drug effects Cyclic AMP Response Element-Binding Protein / metabolism* Down-Regulation / drug effects Down-Regulation / genetics Extracellular Signal-Regulated MAP Kinases / metabolism* Gene Silencing / drug effects JNK Mitogen-Activated Protein Kinases / metabolism* Mice Osteoclasts / cytology Osteoclasts / drug effects Osteoclasts / metabolism* Osteogenesis* / drug effects Phosphorylation / drug effects Protein Kinase Inhibitors / pharmacology RANK Ligand / pharmacology RAW 264.7 Cells Signal Transduction* / drug effects Tartrate-Resistant Acid Phosphatase / metabolism Time Factors p38 Mitogen-Activated Protein Kinases / metabolism*
IF 3.871
Human and Animal Cells RAW 264(RCB0535)