唑来膦酸对破骨细胞分化中钙调蛋白依赖性激酶Ⅱ和Ⅳ基因表达的影响

doi:10.13481/j.1671-587x.20160105

Abstract

Abstract:

Objective: To determine the effects of zoledronate (ZOL)on the osteoclast differention and gene expressions of Ca²⁺/calmodulin-dependent kinase (CaMK)Ⅱ and Ⅳ,and to clarify their mechanisms. Methods: The mouse RAW264.7 cells were used for osteoclast differentiation and the cells were divided into control and ZOL group. The cells in two groups were induced with receptor activatior of nuclear factor κB ligand(RANKL)(50 mg·L^-1)for 5 d,while the cells in ZOL group were also treated with ZOL (1×10^-6mol·L^-1)for 2 d. 5 d later,the cells were collected and the osteoclastogenesis and the gene expressions of CaMKⅡand CaMKⅣ were detected. Results: The number of osteoclasts,the number and size of resorption lacunaes in ZOL group were 33.0±1.0,46.0±3.5,and (4 125.9±674.8)μm², respevtively,which were significantly lower than those in control group (66.6±3.6,86.0±9.2, and 9 418.3μm²±1 260.8μm²)(P<0.05 or P<0.01). Compared with control group,the mRNA and protein levels of CaMKⅡ and CaMKⅣ in ZOL group were also significantly down-regulated (P<0.05); the expression levels of CaMK Ⅱ mRNA and protein were decreased by 39.3% and 58.9％,the expression levels of CaMK Ⅳ mRNA and protein were decreased by 51.7% and 46.8％.The immunofluorescence examination showed that the fluorescence intensities of CaMKⅡ and CaMKⅣ protein in ZOL group were decreased compared with control group(P<0.05 or P<0.01). Conclusion: At stage of multinuclear mature of osteoclasts,ZOL could significantly inhibit the final formation and resorption function of osteoclasts and down-regulate the gene expressions of CaMKⅡ and CaMKⅣ.CaMKⅡ and CaMKⅣ may play an important role in ZOL-induced inhibition of osteoclastogenesis.

Key words: zoledronate, osteoclasts, Ca²⁺/calmodulin-dependent kinase

CLC Number:

Q813

LIU Juanjuan, LI Peng, DONG Wei, FENG Xiaojie, WEN Liming, SUN Hong, QI Mengchun. Effects of zoledronate on gene expressions of calmodulin- dependent kinase Ⅱ and Ⅳ in osteoclast differentiation[J].Journal of Jilin University Medicine Edition, 2016, 42(01): 19-23.

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Effects of zoledronate on gene expressions of calmodulin- dependent kinase Ⅱ and Ⅳ in osteoclast differentiation

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