CaMKII(δ) regulates osteoclastogenesis through ERK, JNK, and p38 MAPKs and CREB signalling pathway

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:508

Article

Lu, Da-Zhuang¹  Dong, Wei¹  Feng, Xiao-Jie¹  Chen, Hui²  Liu, Juan-Juan¹  Wang, Hui¹  Zang, Lu-Yang³  Qi, Meng-Chun¹ 

[1] North China Univ Sci & Technol, Coll Stomatol, Dept Oral & Maxillofacial Surg, 21 Bohai Rd, Tangshan City 063210, Hebei, Peoples R China

[2] North China Univ Sci & Technol, Dept Oral & Maxillofacial Surg, Affiliated Hosp, Tangshan City 063000, Hebei, Peoples R China

[3] Tangshan Gongren Hosp, Dept Endocrinol, Sect 1, Tangshan City 063000, Hebei, Peoples R China

关键词: Calcium/calmodulin-dependent protein kinases;    Osteoclast;    Extracellular signal-regulated kinases;    c-Jun amino-terminal kinases;    p38;    cAMP response element binding protein;   

DOI  :  10.1016/j.mce.2020.110791

来源: Elsevier

【 摘 要 】

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 (8) were upregulated in a time-dependent manner during osteoclast differentiation. CaMKII(delta) gene silencing significantly inhibited osteoclast formation, bone resorption, and expression of osteoclast-related genes, including nuclear factor of activated T cells cl (NFATc1), tartrate-resistant acid phosphatase (TRAP), and c-Src. Furthermore, CaMKII (delta) 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 (delta) gene silencing. Additionally, CaMKII (delta) gene silencing also suppressed RANKL-triggered CREB phosphorylation. Collectively, these data demonstrate the important role of CaMKII (delta) in osteoclastogenesis regulation through JNK, ERK, and p38 MAPKs and CREB pathway.

【 授权许可】

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