RRC ID 43633
著者 Takarada T, Takarada-Iemata M, Takahata Y, Yamada D, Yamamoto T, Nakamura Y, Hinoi E, Yoneda Y.
タイトル Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts.
ジャーナル J Cell Physiol
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 0.1-1 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.
巻・号 227(10)
ページ 3477-87
公開日 2012-10-1
DOI 10.1002/jcp.24048
PMID 22252936
MeSH Alkaline Phosphatase / metabolism Amino Acid Transport Systems / metabolism Animals Bone Marrow Cells / metabolism Bone Marrow Cells / physiology Bone Resorption / genetics Bone Resorption / metabolism Bone Resorption / physiopathology Calcium / metabolism Cell Differentiation / genetics Cell Differentiation / physiology* Cells, Cultured Chondrocytes / metabolism Chondrocytes / physiology Mice Osteoblasts / metabolism Osteoblasts / physiology* Osteoclasts / metabolism Osteoclasts / physiology* Osteogenesis / genetics Osteogenesis / physiology* RNA, Messenger / genetics Racemases and Epimerases / genetics* Racemases and Epimerases / metabolism Rats Rats, Wistar Serine / genetics Serine / metabolism* Transcriptional Activation / genetics Transcriptional Activation / physiology
IF 5.546
引用数 8
WOS 分野 PHYSIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535) MC3T3-E1(RCB1126) ATDC5(RCB0565)