P2X7 receptor knockdown suppresses osteoclast differentiation by inhibiting autophagy and Ca<sup>2+</sup>/calcineurin signaling

Ma,Yonggang; Di,Ran; Zhao,Hongyan; Song,Ruilong; Zou,Hui; Liu,Zongping

doi:10.3892/mmr.2022.12677

P2X7 receptor knockdown suppresses osteoclast differentiation by inhibiting autophagy and Ca²⁺/calcineurin signaling

Authors:
- Yonggang Ma
- Ran Di
- Hongyan Zhao
- Ruilong Song
- Hui Zou
- Zongping Liu
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Affiliations: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China
Published online on: March 10, 2022 https://doi.org/10.3892/mmr.2022.12677
Article Number: 160
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bone is continuously remodeled in a dynamic process maintained by osteoclasts and osteoblasts, and imbalances in the relative activities of these cell types can cause various pathological conditions, including rheumatoid arthritis and osteoporosis. Osteoclasts are multinucleated cells that serve an important role in regulating the development of osteoporosis. Furthermore, P2X7 receptor activation has a vital role in physiological and pathological reactions in bone, including bone disease. Therefore, the present study aimed to investigate the effect of P2X7 receptor on osteoclast differentiation and to explore the underlying molecular mechanism by western blotting and tartrate‑resistant acid phosphatase staining. The results indicated that the expression levels of P2X7 receptor and intracellular Ca2+ concentration levels were very high in mature osteoclasts. Furthermore, P2X7 receptor overexpression increased the number of multinucleated osteoclasts and the expression of osteoclastogenesis‑related proteins. P2X7 receptor overexpression was also associated with downstream activation of Ca²⁺/calcineurin/nuclear factor of activated T cells c1 (NFATc1) signaling and increased expression of autophagy‑related proteins during osteoclast differentiation. By contrast, knockdown of P2X7 receptor exerted the opposite effects. Notably, FK506 (a Ca²⁺/calcineurin/NFATc1 signaling inhibitor) abrogated P2X7 receptor overexpression‑induced osteoclast differentiation and activation of autophagy. Moreover, 3‑MA (an autophagy inhibitor) significantly suppressed P2X7 receptor overexpression‑induced osteoclast differentiation. In conclusion, P2X7 receptor knockdown may suppress osteoclast differentiation by modulating autophagy and the Ca²⁺/calcineurin/NFATc1 signaling pathway.

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