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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: Zhang, Yufeng, Zhang, Sheng, Wang, Yi, Yang, Zhiqiang, Chen, Zhe, Wen, Nengqiao, Yang, Min, Huang, Zan, Xie, Yuanlong, Cai, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608530/
https://www.ncbi.nlm.nih.gov/pubmed/34820053
http://dx.doi.org/10.1155/2021/2896674
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author Zhang, Yufeng
Zhang, Sheng
Wang, Yi
Yang, Zhiqiang
Chen, Zhe
Wen, Nengqiao
Yang, Min
Huang, Zan
Xie, Yuanlong
Cai, Lin
author_facet Zhang, Yufeng
Zhang, Sheng
Wang, Yi
Yang, Zhiqiang
Chen, Zhe
Wen, Nengqiao
Yang, Min
Huang, Zan
Xie, Yuanlong
Cai, Lin
author_sort Zhang, Yufeng
collection PubMed
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.
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spelling pubmed-86085302021-11-23 ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3 Zhang, Yufeng Zhang, Sheng Wang, Yi Yang, Zhiqiang Chen, Zhe Wen, Nengqiao Yang, Min Huang, Zan Xie, Yuanlong Cai, Lin Oxid Med Cell Longev Research Article 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. Hindawi 2021-11-15 /pmc/articles/PMC8608530/ /pubmed/34820053 http://dx.doi.org/10.1155/2021/2896674 Text en Copyright © 2021 Yufeng Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Yufeng
Zhang, Sheng
Wang, Yi
Yang, Zhiqiang
Chen, Zhe
Wen, Nengqiao
Yang, Min
Huang, Zan
Xie, Yuanlong
Cai, Lin
ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608530/
https://www.ncbi.nlm.nih.gov/pubmed/34820053
http://dx.doi.org/10.1155/2021/2896674
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