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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 language | English |
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Pages (from-to) | 1464–1470 |
Number of pages | 7 |
Journal | Journal of Cellular Biochemistry |
Volume | 117 |
Issue number | 6 |
Early online date | 26 Nov 2015 |
DOIs | |
Publication status | Published - 1 Jun 2016 |
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Dive into the research topics of 'Bafilomycin A1 Attenuates Osteoclast Acidification and Formation, Accompanied by Increased Levels of SQSTM1/p62 Protein'. Together they form a unique fingerprint.Projects
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The influence of mutant p62 proteins expressed in Pagets Disease of bone on cell survival & death
Xu, J. (Investigator 01), Walsh, J. (Investigator 02), Rea, S. (Investigator 03), Pavlos, N. (Investigator 04) & Ratajczak, T. (Investigator 05)
NHMRC National Health and Medical Research Council
1/01/12 → 31/12/14
Project: Research