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Osteoclastogenesis is negatively regulated by D ‐serine produced by osteoblasts
Author(s) -
Takarada Takeshi,
TakaradaIemata Mika,
Takahata Yoshifumi,
Yamada Daisuke,
Yamamoto Tomomi,
Nakamura Yukari,
Hinoi Eiichi,
Yoneda Yukio
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24048
Subject(s) - chemistry , microbiology and biotechnology , gene knockdown , extracellular , osteoclast , progenitor cell , osteoblast , serine , biochemistry , in vitro , biology , stem cell , enzyme , gene
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 0.1–1 mM 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.