Interleukin‑17A facilitates osteoclast differentiation and bone resorption via activation of autophagy in mouse bone marrow macrophages

Song,Lu; Tan,Jingyi; Wang,Zhongxiu; Ding,Peihui; Tang,Qi; Xia,Mengjiao; Wei,Yingming; Chen,Lili

doi:10.3892/mmr.2019.10155

Interleukin‑17A facilitates osteoclast differentiation and bone resorption via activation of autophagy in mouse bone marrow macrophages

Authors:
- Lu Song
- Jingyi Tan
- Zhongxiu Wang
- Peihui Ding
- Qi Tang
- Mengjiao Xia
- Yingming Wei
- Lili Chen
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Affiliations: Department of Periodontology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: April 11, 2019 https://doi.org/10.3892/mmr.2019.10155
Pages: 4743-4752
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interleukin 17A (IL‑17A) exerts pleiotropic effects on periodontitis, partially through enhancement of alveolar bone loss. Osteoclasts are the main culprits that absorb alveolar bone. However, studies describing the correlation between IL‑17A and osteoclasts are not conclusive. Previously, autophagy was revealed to be involved in osteoclast differentiation and bone resorption. However, the role of autophagy in IL‑17A‑mediated osteoclast formation is yet to be clarified. In the present study, bone marrow macrophages (BMMs) were treated with or without IL‑17A. 3‑Methyladenine (3‑MA) was applied to inhibit autophagy. Osteoclast formation was detected by tartrate‑resistant acid phosphatase (TRAP) staining, immunofluorescence, and scanning electron microscope. The effects of IL‑17A on osteoclast‑specific genes and autophagy‑related genes during osteoclast differentiation were examined by real‑time quantitative polymerase chain reaction and western blot analysis. Autophagosomes were observed by transmission electron microscope. Hematoxylin and eosin (H&E), and TRAP staining was adopted to assess alveolar bone destruction and the number of osteoclasts, respectively in a rat periodontitis model. Consequently, IL‑17A stimulated osteoclast differentiation and bone resorption of BMMs accompanied by an increase in the mRNA expression of osteoclast‑specific genes. Furthermore, IL‑17A increased the levels of autophagy‑related genes and proteins, and inhibition of autophagy with 3‑MA attenuated the IL‑17A‑mediated osteoclastogenesis. In addition, there was an increase in the number of osteoclasts and alveolar bone resorption with IL‑17A treatment in the periodontitis rat model. Collectively, these findings indicated that IL‑17A facilitated osteoclast differentiation and bone resorption in vitro and in vivo, which may contribute to the understanding of the molecular basis of IL‑17A in alveolar bone destruction and provide insight on the clinical therapeutic targets for periodontitis.

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