Osteoclast stimulatory transmembrane protein (OC‐STAMP), a novel protein induced by RANKL that promotes osteoclast differentiation

Yang, Meilheng; Birnbaum, Mark J.; MacKay, Carole A.; Mason‐Savas, April; Thompson, Benjamin; Odgren, Paul R.

doi:10.1002/jcp.21331

Cited by 119 publications

(137 citation statements)

References 16 publications

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“…(3,21,25) Antibody-mediated block of OC-STAMP reportedly inhibits osteoclast formation and bone resorption. (26,30) Although, OC-STAMP-deficient mononuclear osteoclasts resorb bone, bone-resorbing area per well, as analyzed by pit formation assay, was significantly inhibited in OC-STAMPdeficient osteoclasts compared with WT osteoclasts (Fig. 3C).…”

Section: Oc-stamp Is Required For Osteoclast Cell-cell Fusionmentioning

confidence: 95%

“…(28) Likewise, Car2 regulates proton synthesis, and a subtype of proton pump reportedly functions in cell-cell fusion of osteoclasts and FBGCs. (21) OC-STAMP reportedly regulates osteoclast differentiation, (26) but the function of all three factors in cellcell fusion is not well known.…”

Section: Oc-stamp Is Required For Osteoclast Cell-cell Fusionmentioning

confidence: 99%

“…These observations suggest that OC-STAMP plays a role in cell-cell fusion rather than in cell proliferation. OC-STAMP knockdown by small interfering RNA (siRNA) or short hairpin RNA (shRNA) or by an addition of an OC-STAMP antibody reportedly inhibits formation of TRAPpositive multinuclear cells (26,30) and osteoclast differentiation. (30) However, osteoclast-related genes such as nuclear factor of activated T cell 1 (NFATc1) and c-Fos, which are transcription factors required for osteoclastogenesis, and Cathepsin K, TRAP, and MMP9, which are osteoclast differentiation markers, were all equally expressed in OC-STAMP-deficient osteoclasts (Fig.…”

Section: Oc-stamp Is Required For Osteoclast Cell-cell Fusionmentioning

confidence: 99%

“…OC-STAMP was previously cloned in RANKL-treated RAW264.7 osteoclast precursor cells. (26) Here we isolated OC-STAMP using a subtractive microarray screen between multinuclear osteoclasts and mononuclear macrophages. We then generated OC-STAMPdeficient mice and found that fusion of either osteoclasts or FBGCs was completely abrogated in OC-STAMP-deficient mice.…”

Section: Introductionmentioning

confidence: 99%

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Osteoclast stimulatory transmembrane protein and dendritic cell–specific transmembrane protein cooperatively modulate cell–cell fusion to form osteoclasts and foreign body giant cells

Miyamoto

Suzuki

Miyauchi

et al. 2012

Journal of Bone and Mineral Research

151

135

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Cell-cell fusion is a dynamic phenomenon promoting cytoskeletal reorganization and phenotypic changes. To characterize factors essential for fusion of macrophage lineage cells, we identified the multitransmembrane protein, osteoclast stimulatory transmembrane protein (OC-STAMP), and analyzed its function. OC-STAMP-deficient mice exhibited a complete lack of cell-cell fusion of osteoclasts and foreign body giant cells (FBGCs), both of which are macrophage-lineage multinuclear cells, although expression of dendritic cell specific transmembrane protein (DC-STAMP), which is also essential for osteoclast/FBGC fusion, was normal. Crossing OC-STAMP-overexpressing transgenic mice with OC-STAMP-deficient mice restored inhibited osteoclast and FBGC cell-cell fusion seen in OC-STAMP-deficient mice. Thus, fusogenic mechanisms in macrophage-lineage cells are regulated via OC-STAMP and DC-STAMP. ß

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Section: Oc-stamp Is Required For Osteoclast Cell-cell Fusionmentioning

confidence: 95%

Section: Oc-stamp Is Required For Osteoclast Cell-cell Fusionmentioning

confidence: 99%

Section: Oc-stamp Is Required For Osteoclast Cell-cell Fusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Osteoclast stimulatory transmembrane protein and dendritic cell–specific transmembrane protein cooperatively modulate cell–cell fusion to form osteoclasts and foreign body giant cells

Miyamoto

Suzuki

Miyauchi

et al. 2012

Journal of Bone and Mineral Research

151

135

View full text Add to dashboard Cite

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“…21,22) OC-STAMP, DC-STAMP, ATP6v0d2 and cathepsin K are well-known molecules for fusion and bone resorptive activity. [23][24][25] Integrin ανβ3 is also required for the maintenance of the osteoclast actin cytoskeleton and the control of bone resorption. 26) Our data suggest that purslane significantly inhibited the RANKLinduced expression of c-Fos and NFATc1.…”

Section: Discussionmentioning

confidence: 99%

Purslane Suppresses Osteoclast Differentiation and Bone Resorbing Activity via Inhibition of Akt/GSK3β-c-Fos-NFATc1 Signaling in Vitro and Prevents Lipopolysaccharide-Induced Bone Loss in Vivo

Kim

Kwak

et al. 2015

Biological ^|^ Pharmaceutical Bulletin

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Purslane (Portulaca oleracea L.) is popular as a potherb in many areas of Europe, Asia, and the Mediterranean region and is widely distributed around the globe. It has a wide range of pharmacological effects, such as antibacterial, anti-aging, anti-inflammatory, and anti-oxidative properties. Although the extract of purslane has numerous beneficial pharmacological effects, its effect on osteoclasts remains unknown. We aimed to investigate the anti-osteoclastogenic activity in vitro and in vivo and to elucidate the underlying mechanism. The effect of purslane on the differentiation and function of bone marrow-derived macrophages (BMMs) into osteoclasts was examined using a phenotype assay such as tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining, and pit assay and followed by confirmation by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. To address the effect of purslane in vivo, the inflammatory, lipopolysaccharide (LPS)-induced osteolysis mouse model was chosen. Bone volume and bone microarchitecture were evaluated by microcomputed tomography and histologic analysis. Purslane inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-stimulated osteoclast differentiation accompanied by inhibition of Akt/glycogen synthase kinase 3β (GSK3β) signaling, which could underlie purslane-induced downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) expression levels, transcription factors that regulate osteoclast-specific genes, as well as osteoclast fusion and resorptionrelated molecules. Moreover, in vivo studies further verified the bone protection activity of purslane in the LPS-induced osteolysis animal model. Purslane could exhibit its anti-osteoclastogenic activity by inhibiting Akt/GSK3β-c-Fos-NFATc1 signaling cascades. Therefore, purslane is a potential natural medicine for the treatment of osteoclast-related diseases.Key words purslane (Portulaca oleracea); osteoclast; bone loss; osteoporosis; natural medicine Bone is an important organ that provides mechanical support to soft tissues and maintains blood calcium and phosphate level and hematopoiesis. Both osteoblast-mediated bone formation and osteoclast-mediated resorption contribute to the dynamic remodeling process in bone tissue.1,2) Abnormal activation of osteoclasts attributes to bone loss in many bone destructive diseases including osteoporosis, lytic bone metastases, and rheumatoid arthritis. 1) Accordingly, modulation of osteoclast differentiation and function can be a potent therapeutic target for various bone diseases characterized by excessive bone resorption.Osteoclasts are exclusive bone-resorbing, multinucleated cells formed by the proliferation, differentiation, and fusion of hematopoietic cells belonging to the macrophage lineage. 1,3)When attached to bone matrix, multinucleated osteoclasts polarize their membrane to the bone and secrete protons and lytic enzymes such as cathepsin K into the resorption lacuna surrounded by a tight sealing zone.1)...

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Using osteoclast differentiation as a model for gene discovery in an undergraduate cell biology laboratory

Birnbaum

Picco

Clements

et al. 2010

Biochem Molecular Bio Educ

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A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. The current article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory providing students, within a framework of bone cell biology, with a modern approach to gene discovery. Students are introduced to the topics of bone cells, bone synthesis, bone resorption, and osteoporosis. They then review the theory of microchip gene arrays, and study microchip array data generated during the differentiation of bone-resorbing osteoclasts in vitro. The class selects genes whose expression increases during osteoclastogenesis, and researches them in small groups using web-based bioinformatics tools. Students then go to a biotechnology company website to find and order siRNAs designed to “knockdown” expression of the gene of interest. Students then learn to transfect these siRNAs into osteoclasts, stimulate the cells to differentiate, assay osteoclast differentiation in vitro, and measure specific gene expression using real-time PCR and immunoblotting. Specific siRNA knockdown resulting in a decrease in osteoclastogenesis is indicative of a gene's physiological relevance. The results are analyzed statistically, and presented to the class in groups. In the past two years, students identified several genes essential for optimal osteoclast differentiation, including Myo1d. The students hypothesize that the myo1d protein functions in osteoclasts to deliver important proteins to the cell surface via vesicular transport along microfilaments. Student response to the new course was overwhelmingly positive.

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Osteoclast stimulatory transmembrane protein (OC‐STAMP), a novel protein induced by RANKL that promotes osteoclast differentiation

Cited by 119 publications

References 16 publications

Osteoclast stimulatory transmembrane protein and dendritic cell–specific transmembrane protein cooperatively modulate cell–cell fusion to form osteoclasts and foreign body giant cells

Osteoclast stimulatory transmembrane protein and dendritic cell–specific transmembrane protein cooperatively modulate cell–cell fusion to form osteoclasts and foreign body giant cells

Purslane Suppresses Osteoclast Differentiation and Bone Resorbing Activity via Inhibition of Akt/GSK3β-c-Fos-NFATc1 Signaling in Vitro and Prevents Lipopolysaccharide-Induced Bone Loss in Vivo

Using osteoclast differentiation as a model for gene discovery in an undergraduate cell biology laboratory

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