RANKL-induced TRPV2 expression regulates osteoclastogenesis via calcium oscillations
| Autor: | Koji Okabe, Tetsuomi Nemoto, Kazuko Toh-Goto, Shuji Nakayana, Hiroshi Kajiya, Keiichiro Kimachi, Fujio Okamoto |
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| Rok vydání: | 2010 |
| Předmět: |
musculoskeletal diseases
Ruthenium red ORAI1 Protein Physiology TRPV2 Gene Expression Osteoclasts TRPV Cation Channels TRPV Cell Line Membrane Potentials Mice Transient receptor potential channel chemistry.chemical_compound Osteoclast medicine Animals Calcium Signaling Gene Silencing Stromal Interaction Molecule 1 Bone Resorption Enzyme Inhibitors Molecular Biology Cells Cultured Oligonucleotide Array Sequence Analysis Membrane Glycoproteins NFATC Transcription Factors biology Chemistry Activator (genetics) Macrophages RANK Ligand STIM1 Cell Biology Molecular biology Cell biology medicine.anatomical_structure RANKL Type C Phospholipases biology.protein Calcium Channels |
| Zdroj: | Cell Calcium. 48:260-269 |
| ISSN: | 0143-4160 |
| DOI: | 10.1016/j.ceca.2010.09.010 |
| Popis: | The receptor activator of NFκB ligand (RANKL) induces Ca(2+) oscillations and activates the Nuclear Factor of Activated T cells 1 (NFATc1) during osteoclast differentiation (osteoclastogenesis). Ca(2+) oscillations are an important trigger signal for osteoclastogenesis, however the molecular basis of Ca(2+) permeable influx pathways serving Ca(2+) oscillations has not yet been identified. Using a DNA microarray, we found that Transient Receptor Potential Vanilloid channels 2 (TRPV2) are expressed significantly in RANKL-treated RAW264.7 cells (preosteoclasts) compared to untreated cells. Therefore, we further investigated the expression and functional role of TRPV2 on Ca(2+) oscillations and osteoclastogenesis. We found that RANKL dominantly up-regulates TRPV2 expression in preosteoclasts, and evokes spontaneous Ca(2+) oscillations and a transient inward cation current in a time-dependent manner. TRPV inhibitor ruthenium red and tetracycline-induced TRPV2 silencing significantly decreased both the frequency of Ca(2+) oscillations and the transient inward currents in RANKL-treated preosteoclasts. Silencing of store-operated Ca(2+) entry (SOCE) proteins similarly suppressed both RANKL-induced oscillations and currents in preosteoclasts. Furthermore, suppression of TRPV2 also reduced RANKL-induced NAFTc1 expression, its nuclear translocation, and osteoclastogenesis. In summary, Ca(2+) oscillations in preosteoclasts are triggered by RANKL-dependent TRPV2 and SOCE activation and intracellular Ca(2+) release. Subsequent activation of NFATc1 promotes osteoclastogenesis. |
| Databáze: | OpenAIRE |
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