ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3

Bone resorption diseases, including osteoporosis, are usually caused by excessive osteoclastogenesis. Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian serine/threonine kinase, may participate in the regulation of bone homeostasis and osteolytic metastasis. In this study, ULK1 expression...

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Autores principales:	Yufeng Zhang, Sheng Zhang, Yi Wang, Zhiqiang Yang, Zhe Chen, Nengqiao Wen, Min Yang, Zan Huang, Yuanlong Xie, Lin Cai
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/e1f6bf5629c54ffabc9cd3c505c05870
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spelling	oai:doaj.org-article:e1f6bf5629c54ffabc9cd3c505c058702021-11-29T00:56:19ZULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK31942-099410.1155/2021/2896674https://doaj.org/article/e1f6bf5629c54ffabc9cd3c505c058702021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/2896674https://doaj.org/toc/1942-0994Bone resorption diseases, including osteoporosis, are usually caused by excessive osteoclastogenesis. Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian serine/threonine kinase, may participate in the regulation of bone homeostasis and osteolytic metastasis. In this study, ULK1 expression during osteoclastogenesis was detected with RT-PCR. We knocked down or overexpressed ULK1 through siRNA or lentiviral transduction in bone marrow macrophage (BMM). TRAP and phalloidin staining were performed to detect the osteoclastogenesis activity. Ovariectomized (OVX) mouse model of osteoporosis and a mouse of model osteoclast-induced bone resorption were applied to explore the role of ULK1 in bone resorption in vivo. The results showed that ULK1 expression was downregulated during osteoclast differentiation and was clinically associated with osteoporosis. ULK1 inhibited osteoclast differentiation in vitro. Knockdown of ULK1 expression activated phosphorylation of c-Jun N-terminal kinase (JNK) and spleen tyrosine kinase (Syk). Docking protein 3 (DOK3) was coexpressed with ULK1 during osteoclastogenesis. Downregulation of DOK3 offsets the effect of ULK1 on osteoclastogenesis and induced phosphorylation of JNK and Syk. Activation of ULK1 impeded bone loss in OVX mice with osteoporosis. Additionally, upregulation of ULK1 inhibited osteoclast-induced bone resorption in vivo. Therefore, our study reveals a novel ULK1/DOK3/Syk axis that regulates osteoclast differentiation and bone resorption, and targeting ULK1 is a potential therapeutic strategy for osteoporosis.Yufeng ZhangSheng ZhangYi WangZhiqiang YangZhe ChenNengqiao WenMin YangZan HuangYuanlong XieLin CaiHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Yufeng Zhang Sheng Zhang Yi Wang Zhiqiang Yang Zhe Chen Nengqiao Wen Min Yang Zan Huang Yuanlong Xie Lin Cai ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3
description	Bone resorption diseases, including osteoporosis, are usually caused by excessive osteoclastogenesis. Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian serine/threonine kinase, may participate in the regulation of bone homeostasis and osteolytic metastasis. In this study, ULK1 expression during osteoclastogenesis was detected with RT-PCR. We knocked down or overexpressed ULK1 through siRNA or lentiviral transduction in bone marrow macrophage (BMM). TRAP and phalloidin staining were performed to detect the osteoclastogenesis activity. Ovariectomized (OVX) mouse model of osteoporosis and a mouse of model osteoclast-induced bone resorption were applied to explore the role of ULK1 in bone resorption in vivo. The results showed that ULK1 expression was downregulated during osteoclast differentiation and was clinically associated with osteoporosis. ULK1 inhibited osteoclast differentiation in vitro. Knockdown of ULK1 expression activated phosphorylation of c-Jun N-terminal kinase (JNK) and spleen tyrosine kinase (Syk). Docking protein 3 (DOK3) was coexpressed with ULK1 during osteoclastogenesis. Downregulation of DOK3 offsets the effect of ULK1 on osteoclastogenesis and induced phosphorylation of JNK and Syk. Activation of ULK1 impeded bone loss in OVX mice with osteoporosis. Additionally, upregulation of ULK1 inhibited osteoclast-induced bone resorption in vivo. Therefore, our study reveals a novel ULK1/DOK3/Syk axis that regulates osteoclast differentiation and bone resorption, and targeting ULK1 is a potential therapeutic strategy for osteoporosis.
format	article
author	Yufeng Zhang Sheng Zhang Yi Wang Zhiqiang Yang Zhe Chen Nengqiao Wen Min Yang Zan Huang Yuanlong Xie Lin Cai
author_facet	Yufeng Zhang Sheng Zhang Yi Wang Zhiqiang Yang Zhe Chen Nengqiao Wen Min Yang Zan Huang Yuanlong Xie Lin Cai
author_sort	Yufeng Zhang
title	ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3
title_short	ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3
title_full	ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3
title_fullStr	ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3
title_full_unstemmed	ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3
title_sort	ulk1 suppresses osteoclast differentiation and bone resorption via inhibiting syk-jnk through dok3
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/e1f6bf5629c54ffabc9cd3c505c05870
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ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3

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