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VNUT/SLC17A9, a vesicular nucleotide transporter, regulates osteoblast differentiation.

Authors
  • Inoue, Asako1
  • Nakao-Kuroishi, Kayoko1
  • Kometani-Gunjigake, Kaori1
  • Mizuhara, Masahiro1
  • Shirakawa, Tomohiko1
  • Ito-Sago, Misa1
  • Yasuda, Kazuma1
  • Nakatomi, Mitsushiro2
  • Matsubara, Takuma3
  • Tada-Shigeyama, Yukiyo4
  • Morikawa, Kazumasa5
  • Kokabu, Shoichiro3
  • Kawamoto, Tatsuo1
  • 1 Division of Orofacial Functions and Orthodontics, Department of Health Improvement, Kyushu Dental University, Kitakyushu-shi, Japan. , (Japan)
  • 2 Division of Anatomy, Department of Health Improvement, Kyushu Dental University, Kitakyushu-shi, Japan. , (Japan)
  • 3 Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu-shi, Japan. , (Japan)
  • 4 Division of Dental Anesthesiology, Department of Science of Physical Functions, Kyushu Dental University, Kitakyushu-shi, Japan. , (Japan)
  • 5 Division of Pediatric and Special Care Dentistry, Department of Developmental Oral Health Science, School of Dentistry, Iwate Medical University, Morioka, Japan. , (Japan)
Type
Published Article
Journal
FEBS Open Bio
Publisher
Wiley (John Wiley & Sons)
Publication Date
Aug 01, 2020
Volume
10
Issue
8
Pages
1612–1623
Identifiers
DOI: 10.1002/2211-5463.12918
PMID: 32592329
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Osteoblasts release adenosine triphosphate (ATP) out of the cell following mechanical stress. Although it is well established that extracellular ATP affects bone metabolism via P2 receptors [such as purinergic receptor P2X7 (P2X7R) and purinergic receptor P2Y2 (P2Y2R)], the mechanism of ATP release from osteoblasts remains unknown. Recently, a vesicular nucleotide transporter [VNUT, solute carrier family 17 member 9 (SLC17A9)] that preserves ATP in vesicles has been identified. The purpose of this study was to elucidate the role of VNUT in osteoblast bone metabolism. mRNA and protein expression of VNUT were confirmed in mouse bone and in osteoblasts by quantitative real-time PCR (qPCR) and immunohistochemistry. Next, when compressive force was applied to MC3T3-E1 cells by centrifugation, the expression of Slc17a9, P2x7r, and P2y2r was increased concomitant with an increase in extracellular ATP levels. Furthermore, compressive force decreased the osteoblast differentiation capacity of MC3T3-E1 cells. shRNA knockdown of Slc17a9 in MC3T3-E1 cells reduced levels of extracellular ATP and also led to increased osteoblast differentiation after the application of compressive force as assessed by qPCR analysis of osteoblast markers such as Runx2, Osterix, and alkaline phosphatase (ALP) as well as ALP activity. Consistent with these observations, knockdown of P2x7r or P2y2r by siRNA partially rescued the downregulation of osteoblast differentiation markers, caused by mechanical loading. In conclusion, our results demonstrate that VNUT is expressed in osteoblasts and that VNUT inhibits osteoblast differentiation in response to compressive force by mechanisms related to ATP release and P2X7R and/or P2Y2R activity. © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

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