Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts

Takeshi Takarada, Mika Takarada-Iemata, Yoshifumi Takahata, Daisuke Yamada, Tomomi Yamamoto, Yukari Kyumoto, Eiichi Hinoi, Yukio Yoneda

Research output: Contribution to journalArticle

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Abstract

We have shown the functional expression by chondrocytes of serine racemase (SR) which is responsible for the synthesis of D-serine (Ser) from L-Ser in cartilage. In this study, we evaluated the possible functional expression of SR by bone-forming osteoblasts and bone-resorbing osteoclasts. Expression of SR mRNA was seen in osteoblasts localized at the cancellous bone surface in neonatal rat tibial sections and in cultured rat calvarial osteoblasts endowed to release D-Ser into extracellular medium, but not in cultured osteoclasts differentiated from murine bone marrow progenitor cells. Sustained exposure to D-Ser failed to significantly affect alkaline phosphatase activity and Ca 2+ accumulation in cultured osteoblasts, but significantly inhibited differentiation and maturation in a concentration-dependent manner at a concentration range of 0.1-1mM without affecting cellular survival in cultured osteoclasts. By contrast, L-Ser promoted osteoclastic differentiation in a manner sensitive to the inhibition by D-Ser. Matured osteoclasts expressed mRNA for the amino acid transporter B 0,+ (ATB 0,+) and the system alanine, serine, and cysteine amino acid transporter-2 (ASCT2), which are individually capable of similarly incorporating extracellular L- and D-Ser. Knockdown of these transporters by siRNA prevented both the promotion by L-Ser and the inhibition by D-Ser of osteoclastic differentiation in pre-osteoclastic RAW264.7 cells. These results suggest that D-Ser may play a pivotal role in osteoclastogenesis through a mechanism related to the incorporation mediated by both ATB 0,+ and ASCT2 of serine enantiomers in osteoclasts after the synthesis and subsequent release from adjacent osteoblasts. J. Cell. Physiol. 227: 3477-3487, 2012. © 2012 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)3477-3487
Number of pages11
JournalJournal of cellular physiology
Volume227
Issue number10
DOIs
Publication statusPublished - Oct 1 2012

Fingerprint

Osteoblasts
Osteogenesis
Serine
Osteoclasts
Amino Acid Transport Systems
Bone
Alanine
Cysteine
Rats
Bone and Bones
Messenger RNA
Enantiomers
Cartilage
Chondrocytes
Bone Marrow Cells
Small Interfering RNA
Alkaline Phosphatase
Stem Cells

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Takarada, T., Takarada-Iemata, M., Takahata, Y., Yamada, D., Yamamoto, T., Kyumoto, Y., ... Yoneda, Y. (2012). Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts. Journal of cellular physiology, 227(10), 3477-3487. https://doi.org/10.1002/jcp.24048

Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts. / Takarada, Takeshi; Takarada-Iemata, Mika; Takahata, Yoshifumi; Yamada, Daisuke; Yamamoto, Tomomi; Kyumoto, Yukari; Hinoi, Eiichi; Yoneda, Yukio.

In: Journal of cellular physiology, Vol. 227, No. 10, 01.10.2012, p. 3477-3487.

Research output: Contribution to journalArticle

Takarada, T, Takarada-Iemata, M, Takahata, Y, Yamada, D, Yamamoto, T, Kyumoto, Y, Hinoi, E & Yoneda, Y 2012, 'Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts', Journal of cellular physiology, vol. 227, no. 10, pp. 3477-3487. https://doi.org/10.1002/jcp.24048
Takarada T, Takarada-Iemata M, Takahata Y, Yamada D, Yamamoto T, Kyumoto Y et al. Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts. Journal of cellular physiology. 2012 Oct 1;227(10):3477-3487. https://doi.org/10.1002/jcp.24048
Takarada, Takeshi ; Takarada-Iemata, Mika ; Takahata, Yoshifumi ; Yamada, Daisuke ; Yamamoto, Tomomi ; Kyumoto, Yukari ; Hinoi, Eiichi ; Yoneda, Yukio. / Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts. In: Journal of cellular physiology. 2012 ; Vol. 227, No. 10. pp. 3477-3487.
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