Zoledronic acid inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways

Huang,Xiao‑Lin; Huang,Lie‑Yu; Cheng,Yu‑Ting; Li,Fang; Zhou,Qian; Wu,Chao; Shi,Qian‑Hui; Guan,Zhi‑Zhong; Liao,Jian; Hong,Wei

doi:10.3892/ijmm.2019.4207

Zoledronic acid inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways

Authors:
- Xiao‑Lin Huang
- Lie‑Yu Huang
- Yu‑Ting Cheng
- Fang Li
- Qian Zhou
- Chao Wu
- Qian‑Hui Shi
- Zhi‑Zhong Guan
- Jian Liao
- Wei Hong
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Affiliations: School/Hospital of Stomatology and Key Laboratory of Endemic and Ethnic Diseases, Guizhou Medical University, Ministry of Education, Guiyang, Guizhou 550004, P.R. China, Department of Medical Psychology, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
Published online on: May 23, 2019 https://doi.org/10.3892/ijmm.2019.4207
Pages: 582-592
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It is well known that extensive osteoclast formation plays a key role in osteoporosis in post‑menopausal women and the elderly. The suppression of extensive osteoclastogenesis and bone resorption may be an effective preventive strategy for osteoporosis. Zoledronic acid (ZOL) has been indicated to play an essential role in regulating bone mineral density and has already been used in large clinical trials. However, the effects of ZOL on osteoclastogenesis remain to be fully elucidated. Therefore, the present study aimed to determine the effects of ZOL on osteoclastogenesis, and to explore the corresponding signalling pathways. By using a cell viability assay, as well as in vitro osteoclastogenesis, immunofluorescence and resorption pit assays, we demonstrated that ZOL (0.1‑5 µM) suppressed receptor activator of nuclear factor‑κB ligand (RANKL)‑induced osteoclast differentiation and bone resorptive activity. Furthermore, western blot analysis and reverse transcription‑quantitative PCR indicated that ZOL inhibited the RANKL‑induced activation of NF‑κB and the phosphorylation of JNK in RAW264.7 cells, and subsequently decreased the expression of osteoclastogenesis‑associated genes, including calcitonin receptor, tartrate‑resistant acid phosphatase and dendritic cell‑specific transmembrane protein. ZOL inhibited osteoclast formation and resorption in vitro by specifically suppressing NF‑κB and JNK signalling. On the whole, the findings of this study indicate that ZOL may serve as a potential agent for the treatment of osteoclast‑associated diseases, including osteoporosis.

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