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PMID:23980096

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Citation

Maruyama, K, Uematsu, S, Kondo, T, Takeuchi, O, Martino, MM, Kawasaki, T and Akira, S (2013) Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP. J. Exp. Med. 210:1947-60

Abstract

Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors in response to receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). We found that RANKL induced expression of the DExD/H helicase family corepressor strawberry notch homologue 2 (Sbno2). Previous in vitro studies showed that Sbno2 is induced by IL-10 and is involved in NF-κB repression. However, the role of Sbno2 in vivo and its pleiotropic functions are unknown. Sbno2 gene targeting resulted in normal NF-κB activation by TLR ligands. However, Sbno2-deficient mice exhibited increased bone mass due to impaired osteoclast fusion. Expression of dendritic cell-specific transmembrane protein (DC-STAMP), a critical player in osteoclast fusion, was significantly attenuated, and cell fusion of Sbno2-deficient osteoclasts was rescued by DC-STAMP. Sbno2 directly bound to T cell acute lymphocytic leukemia 1 (Tal1) and attenuated its inhibition of DC-STAMP expression, leading to activation of the DC-STAMP promoter by microphthalmia-associated transcription factor (MITF). Thus, Sbno2 plays a pivotal role in bone homeostasis in vivo by fine-tuning osteoclast fusion.

Links

PubMed PMC3782043 Online version:10.1084/jem.20130512

Keywords

Animals; Bone and Bones/metabolism; Bone and Bones/pathology; Cell Differentiation/genetics; Enzyme Activation/genetics; Female; Gene Expression Regulation; Giant Cells; Male; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Mice, Knockout; NF-kappa B/metabolism; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Osteoblasts/cytology; Osteoblasts/metabolism; Osteoclasts/cytology; Osteoclasts/metabolism; Osteogenesis/genetics; Phenotype; Repressor Proteins/genetics; Repressor Proteins/metabolism; Signal Transduction; Toll-Like Receptors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TNF11

acts_upstream_of_or_within

GO:2001206: positive regulation of osteoclast development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NFAC1

enables

GO:0003677: DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FOS

enables

GO:0000978: RNA polymerase II cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SPI1

enables

GO:0000978: RNA polymerase II cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TAL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q7TNB8

F

Seeded From UniProt

complete

MOUSE:TAL1

enables

GO:0000978: RNA polymerase II cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:NFKB1

enables

GO:0003677: DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:MITF

enables

GO:0000978: RNA polymerase II cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SBNO2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P22091

F

Seeded From UniProt

complete

MOUSE:SBNO2

acts_upstream_of_or_within

GO:0030316: osteoclast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5551983

P

Seeded From UniProt

complete

MOUSE:SBNO2

acts_upstream_of_or_within

GO:0030282: bone mineralization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5551983

P

Seeded From UniProt

complete

MOUSE:SBNO2

acts_upstream_of_or_within

GO:0061430: bone trabecula morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5551983

P

Seeded From UniProt

complete

MOUSE:SBNO2

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5551983

P

Seeded From UniProt

complete

MOUSE:SBNO2

acts_upstream_of_or_within

GO:0072675: osteoclast fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5551983

P

Seeded From UniProt

complete

MOUSE:SBNO2

acts_upstream_of_or_within

GO:0072674: multinuclear osteoclast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5551983

P

Seeded From UniProt

complete

MOUSE:DCSTP

acts_upstream_of_or_within

GO:0072675: osteoclast fusion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:JAG1

acts_upstream_of_or_within

GO:0045669: positive regulation of osteoblast differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SPI1

enables

GO:0000978: RNA polymerase II proximal promoter sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:NFKB1

enables

GO:0003677: DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:MITF

enables

GO:0000978: RNA polymerase II proximal promoter sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FOS

enables

GO:0000978: RNA polymerase II proximal promoter sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

Notes

See also

References

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