Osteoclast stimulatory transmembrane protein (OC‐STAMP), a novel protein induced by RANKL that promotes osteoclast differentiation
Identifieur interne : 006293 ( Main/Exploration ); précédent : 006292; suivant : 006294Osteoclast stimulatory transmembrane protein (OC‐STAMP), a novel protein induced by RANKL that promotes osteoclast differentiation
Auteurs : Meiheng Yang [États-Unis] ; Mark J. Birnbaum [États-Unis] ; Carole A. Mackay [États-Unis] ; April Mason-Savas [États-Unis] ; Benjamin Thompson [États-Unis] ; Paul R. Odgren [États-Unis]Source :
- Journal of Cellular Physiology [ 0021-9541 ] ; 2008-05.
English descriptors
- KwdEn :
- Amino, Amino acid level, Amino acid region, Amino acid sequences, Amino acids, Attoglow chemiluminescent substrate, Bone environment, Bone surface, Cdna, Cell biology, Cell cultures, Cellular physiology, Contract grant number, Contract grant sponsor, Control serum, Dendritic cells, Differentiation, Domain database, Ethidium bromide, Family consensus, Family consensus sequence, Havana vega, Knockout mice, Large numbers, Michigan diagnostics, Moderate osteopetrosis, Mononuclear, Mononuclear cell fusion, Mononuclear cells, More nuclei, Mouse, Mouse sequence, Mrna, Mrna level, Mrna levels, Multinucleated, Multinucleated cells, Multinucleated osteoclast formation, Multinucleated osteoclasts, Multipass transmembrane protein, Multiple wells, National institutes, Negative control, Negative control sirna, Northern blot, Odgren, Osteoclast, Osteoclast differentiation, Osteoclast precursor fusion, Other proteins, Overexpression, Periosteal cells, Physiology, Rankl, Rankl treatment, Resorb bone, Roche diagnostics, Sequence analysis, Several gaps, Similar results, Sirna, Spleen cells, Transfected, Transmembrane, Transmembrane helices, Transmembrane helix, Transmembrane protein, Trap expression, Western blot.
- Teeft :
- Amino, Amino acid level, Amino acid region, Amino acid sequences, Amino acids, Attoglow chemiluminescent substrate, Bone environment, Bone surface, Cdna, Cell biology, Cell cultures, Cellular physiology, Contract grant number, Contract grant sponsor, Control serum, Dendritic cells, Differentiation, Domain database, Ethidium bromide, Family consensus, Family consensus sequence, Havana vega, Knockout mice, Large numbers, Michigan diagnostics, Moderate osteopetrosis, Mononuclear, Mononuclear cell fusion, Mononuclear cells, More nuclei, Mouse, Mouse sequence, Mrna, Mrna level, Mrna levels, Multinucleated, Multinucleated cells, Multinucleated osteoclast formation, Multinucleated osteoclasts, Multipass transmembrane protein, Multiple wells, National institutes, Negative control, Negative control sirna, Northern blot, Odgren, Osteoclast, Osteoclast differentiation, Osteoclast precursor fusion, Other proteins, Overexpression, Periosteal cells, Physiology, Rankl, Rankl treatment, Resorb bone, Roche diagnostics, Sequence analysis, Several gaps, Similar results, Sirna, Spleen cells, Transfected, Transmembrane, Transmembrane helices, Transmembrane helix, Transmembrane protein, Trap expression, Western blot.
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. J. Cell. Physiol. 215: 497–505, 2008. © 2007 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/jcp.21331
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en">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. J. Cell. Physiol. 215: 497–505, 2008. © 2007 Wiley‐Liss, Inc.</div>
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