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Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells
Published on: July 16, 2013
Ca2+ stimulates COX-2 expression through calcium-sensing receptor in fibroblasts
Sachie Ogata1, Yasutaka Kubota, Shinji Satoh
1Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Biochemical and Biophysical Research Communications
|November 14, 2006
Summary
Jaw cyst fibroblasts express the calcium-sensing receptor (CasR). Elevated extracellular calcium activates CasR, increasing cyclooxygenase-2 (COX-2) expression via specific kinase pathways.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Jaw cysts are pathological cavities within the jawbone.
- Fibroblasts play a role in tissue remodeling and inflammation.
- The calcium-sensing receptor (CasR) is involved in various cellular processes.
Purpose of the Study:
- To investigate the role of the calcium-sensing receptor (CasR) in jaw cyst fibroblasts.
- To determine the signaling pathways involved in extracellular calcium-induced responses in these cells.
- To explore the relationship between CasR activation and cyclooxygenase-2 (COX-2) expression.
Main Methods:
- Fibroblast isolation from jaw cysts.
- Measurement of intracellular calcium levels using fluo-3 fluorescence.
- Assay of inositol(1,4,5)trisphosphate production.
- Western blotting for protein kinase C, COX-2, ERK1/2, p38 MAPK, and JNK.
- Quantitative real-time PCR for COX-2 mRNA expression.
- Measurement of prostaglandin E(2) secretion.
- Pharmacological inhibition of phospholipase C and specific kinases.
Main Results:
- Jaw cyst fibroblasts express CasR.
- Elevated extracellular calcium ([Ca(2+)](o)) increased intracellular calcium, inositol(1,4,5)trisphosphate production, and activated protein kinase C.
- U-73122 (a phospholipase C inhibitor) attenuated these Ca(2+)-induced effects.
- [Ca(2+)](o) enhanced COX-2 mRNA and protein expression, and prostaglandin E(2) secretion.
- Neomycin (a CasR activator) increased COX-2 mRNA expression.
- Elevated [Ca(2+)](o) induced phosphorylation of ERK1/2, p38 MAPK, and JNK.
- Inhibitors of ERK1/2, p38 MAPK, and JNK attenuated Ca(2+)-induced COX-2 mRNA expression.
Conclusions:
- Jaw cyst fibroblasts possess functional CasR.
- Elevated extracellular calcium stimulates COX-2 expression and prostaglandin E(2) production in these cells.
- The signaling pathway involves phospholipase C, ERK1/2, p38 MAPK, and JNK activation.
- CasR activation by elevated extracellular calcium represents a potential mechanism for regulating inflammatory mediators in jaw cyst pathogenesis.
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