Bafilomycin A1 Attenuates Osteoclast Acidification and Formation, Accompanied by Increased Levels of SQSTM1/p62 Protein

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Abstract

Vacuolar proton pump H+-adenosine triphosphatases (V-ATPases) play an important role in osteoclast function. Further understanding of the cellular and molecular mechanisms of V-ATPase inhibition is vital for the development of anti-resorptive drugs specifically targeting osteoclast V-ATPases. In this study, we observed that bafilomycin A1, a naturally-occurring inhibitor of V-ATPases, increased the protein level of SQSTM1/p62, a known negative regulator of osteoclast formation. Consistently, we found that bafilomycin A1 diminishes the intracellular accumulation of the acidotropic probe lysotracker in osteoclast-like cells; indicative of reduced acidification. Further, bafilomycin A1 inhibits osteoclast formation with attenuation of cell fusion and multi-nucleation of osteoclast-like cells during osteoclast differentiation. Taken together, these data indicate that bafilomycin A1 attenuates osteoclast differentiation in part via increased levels of SQSTM1/p62 protein, providing further mechanistic insight into the effect of V-ATPase inhibition in osteoclasts. J. Cell. Biochem. 117: 1464–1470, 2016. © 2015 Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)1464–1470
JournalJournal of Cellular Biochemistry
Volume117
Issue number6
Early online date26 Nov 2015
DOIs
Publication statusPublished - Jun 2016

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Acidification
Osteoclasts
Adenosine Triphosphatases
Proton Pumps
Proteins
bafilomycin A1
Cell Fusion
Proton Pump Inhibitors
Drug Delivery Systems
Nucleation
Fusion reactions

Cite this

@article{969d03e93c354db38bfa43fa05f7e346,
title = "Bafilomycin A1 Attenuates Osteoclast Acidification and Formation, Accompanied by Increased Levels of SQSTM1/p62 Protein",
abstract = "Vacuolar proton pump H+-adenosine triphosphatases (V-ATPases) play an important role in osteoclast function. Further understanding of the cellular and molecular mechanisms of V-ATPase inhibition is vital for the development of anti-resorptive drugs specifically targeting osteoclast V-ATPases. In this study, we observed that bafilomycin A1, a naturally-occurring inhibitor of V-ATPases, increased the protein level of SQSTM1/p62, a known negative regulator of osteoclast formation. Consistently, we found that bafilomycin A1 diminishes the intracellular accumulation of the acidotropic probe lysotracker in osteoclast-like cells; indicative of reduced acidification. Further, bafilomycin A1 inhibits osteoclast formation with attenuation of cell fusion and multi-nucleation of osteoclast-like cells during osteoclast differentiation. Taken together, these data indicate that bafilomycin A1 attenuates osteoclast differentiation in part via increased levels of SQSTM1/p62 protein, providing further mechanistic insight into the effect of V-ATPase inhibition in osteoclasts. J. Cell. Biochem. 117: 1464–1470, 2016. {\circledC} 2015 Wiley Periodicals, Inc.",
author = "Sipin Zhu and Sarah Rea and Cheng, {Tak Sum} and Feng, {Hao Tian} and John Walsh and Tom Ratajczak and Jennifer Tickner and Nathan Pavlos and H Xu and Jiake Xu",
year = "2016",
month = "6",
doi = "10.1002/jcb.25442",
language = "English",
volume = "117",
pages = "1464–1470",
journal = "Journal of Cellular Biochemistry",
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}

TY - JOUR

T1 - Bafilomycin A1 Attenuates Osteoclast Acidification and Formation, Accompanied by Increased Levels of SQSTM1/p62 Protein

AU - Zhu, Sipin

AU - Rea, Sarah

AU - Cheng, Tak Sum

AU - Feng, Hao Tian

AU - Walsh, John

AU - Ratajczak, Tom

AU - Tickner, Jennifer

AU - Pavlos, Nathan

AU - Xu, H

AU - Xu, Jiake

PY - 2016/6

Y1 - 2016/6

N2 - Vacuolar proton pump H+-adenosine triphosphatases (V-ATPases) play an important role in osteoclast function. Further understanding of the cellular and molecular mechanisms of V-ATPase inhibition is vital for the development of anti-resorptive drugs specifically targeting osteoclast V-ATPases. In this study, we observed that bafilomycin A1, a naturally-occurring inhibitor of V-ATPases, increased the protein level of SQSTM1/p62, a known negative regulator of osteoclast formation. Consistently, we found that bafilomycin A1 diminishes the intracellular accumulation of the acidotropic probe lysotracker in osteoclast-like cells; indicative of reduced acidification. Further, bafilomycin A1 inhibits osteoclast formation with attenuation of cell fusion and multi-nucleation of osteoclast-like cells during osteoclast differentiation. Taken together, these data indicate that bafilomycin A1 attenuates osteoclast differentiation in part via increased levels of SQSTM1/p62 protein, providing further mechanistic insight into the effect of V-ATPase inhibition in osteoclasts. J. Cell. Biochem. 117: 1464–1470, 2016. © 2015 Wiley Periodicals, Inc.

AB - Vacuolar proton pump H+-adenosine triphosphatases (V-ATPases) play an important role in osteoclast function. Further understanding of the cellular and molecular mechanisms of V-ATPase inhibition is vital for the development of anti-resorptive drugs specifically targeting osteoclast V-ATPases. In this study, we observed that bafilomycin A1, a naturally-occurring inhibitor of V-ATPases, increased the protein level of SQSTM1/p62, a known negative regulator of osteoclast formation. Consistently, we found that bafilomycin A1 diminishes the intracellular accumulation of the acidotropic probe lysotracker in osteoclast-like cells; indicative of reduced acidification. Further, bafilomycin A1 inhibits osteoclast formation with attenuation of cell fusion and multi-nucleation of osteoclast-like cells during osteoclast differentiation. Taken together, these data indicate that bafilomycin A1 attenuates osteoclast differentiation in part via increased levels of SQSTM1/p62 protein, providing further mechanistic insight into the effect of V-ATPase inhibition in osteoclasts. J. Cell. Biochem. 117: 1464–1470, 2016. © 2015 Wiley Periodicals, Inc.

U2 - 10.1002/jcb.25442

DO - 10.1002/jcb.25442

M3 - Article

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EP - 1470

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

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ER -