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PMID:18064667

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Citation

Yang, M, Birnbaum, MJ, MacKay, CA, Mason-Savas, A, Thompson, B and Odgren, PR (2008) Osteoclast stimulatory transmembrane protein (OC-STAMP), a novel protein induced by RANKL that promotes osteoclast differentiation. J. Cell. Physiol. 215:497-505

Abstract

Microarray and real-time RT-PCR were used to examine expression changes in primary bone marrow cells and RAW 264.7 cells in response to RANKL. In silico sequence analysis was performed on a novel gene which we designate OC-STAMP. Specific siRNA and antibodies were used to inhibit OC-STAMP RNA and protein, respectively, and tartrate-resistant acid phosphatase (TRAP)+ multinucleated osteoclasts were counted. Antibodies were used to probe bone tissues and western blots of RAW cell extracts +/- RANKL. cDNA overexpression constructs were transfected into RAW cells and the effect on RANKL-induced differentiation was studied. OC-STAMP was very strongly up-regulated during osteoclast differentiation. Northern blots and sequence analysis revealed two transcripts of 2 and 3.7 kb differing only in 3'UTR length, consistent with predictions from genome sequence. The mRNA encodes a 498 amino acid, multipass transmembrane protein that is highly conserved in mammals. It has little overall homology to other proteins. The carboxy-terminal 193 amino acids, however, are significantly similar to the DC-STAMP family consensus sequence. DC-STAMP is a transmembrane protein required for osteoclast precursor fusion. Knockdown of OC-STAMP mRNA by siRNA and protein inhibition by antibodies significantly suppressed the formation of TRAP+, multinucleated cells in differentiating osteoclast cultures, with many TRAP+ mononuclear cells present. Conversely, overexpression of OC-STAMP increased osteoclastic differentiation of RAW 264.7 cells. We conclude that OC-STAMP is a previously unknown, RANKL-induced, multipass transmembrane protein that promotes the formation of multinucleated osteoclasts.

Links

PubMed PMC2762860 Online version:10.1002/jcp.21331

Keywords

Acid Phosphatase/metabolism; Amino Acid Sequence; Animals; Antibodies/pharmacology; Bone Marrow Cells/cytology; Bone Marrow Cells/metabolism; Bone and Bones/metabolism; Cell Differentiation/drug effects; Cell Differentiation/physiology; Cell Nucleus/ultrastructure; Cells, Cultured; Immunohistochemistry; Isoenzymes/metabolism; Membrane Proteins/antagonists & inhibitors; Membrane Proteins/genetics; Membrane Proteins/metabolism; Membrane Proteins/physiology; Mice; Mice, Knockout; Microarray Analysis; Molecular Sequence Data; Osteoclasts/cytology; Osteoclasts/drug effects; Osteoclasts/metabolism; RANK Ligand/pharmacology; RNA, Messenger/metabolism; RNA, Small Interfering/pharmacology; Rats; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis; Transfection; Up-Regulation

Significance

Annotations

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

MOUSE:OCSTP

involved_in

GO:0045672: positive regulation of osteoclast differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:OCSTP

involved_in

GO:0071356: cellular response to tumor necrosis factor

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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