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.

中文翻译：

---

CaMKII（δ）通过ERK，JNK和p38 MAPK和CREB信号通路调节破骨细胞生成。

钙/钙调蛋白依赖性蛋白激酶（CaMK）是介导钙信号传递的一组重要分子，已被证明参与破骨细胞生成的调控。CaMKII是CaMKs的一种亚型，在破骨细胞分化过程中表达，但其在破骨细胞生成调控中的作用仍存在争议。在本研究中，我们发现破骨细胞分化过程中CaMKII（δ）的mRNA和蛋白水平均呈时间依赖性上调。CaMKII（δ）基因沉默显着抑制破骨细胞形成，骨吸收和破骨细胞相关基因的表达，包括活化T细胞c1（NFATc1），抗酒石酸酸性磷酸酶（TRAP）和c-Src的核因子。此外，CaMKII（δ）基因沉默下调了丝裂原激活的蛋白激酶（MAPK）的磷酸化，包括JNK，ERK和p38，后者被RANKL瞬时激活。ERK，JNK和p38的特异性抑制剂还显着抑制破骨细胞相关基因的表达，破骨细胞形成和骨吸收，例如CaMKII（δ）基因沉默。此外，CaMKII（δ）基因沉默也抑制了RANKL触发的CREB磷酸化。这些数据共同证明了CaMKII（δ）通过JNK，ERK和p38 MAPK和CREB途径在破骨细胞生成调控中的重要作用。此外，CaMKII（δ）基因沉默也抑制了RANKL触发的CREB磷酸化。这些数据共同证明了CaMKII（δ）通过JNK，ERK和p38 MAPK和CREB途径在破骨细胞生成调控中的重要作用。此外，CaMKII（δ）基因沉默也抑制了RANKL触发的CREB磷酸化。这些数据共同证明了CaMKII（δ）通过JNK，ERK和p38 MAPK和CREB途径在破骨细胞生成调控中的重要作用。