Abstract
Parathyroid hormone (PTH) stimulates both bone formation and resorption by activating diverse osteoblast signalling pathways. Upstream signalling for PTH stimulation of protein kinase C-α (PKCα) membrane translocation and subsequent expression of the pro-resorptive cytokine interleukin-6 (IL-6) was investigated in UMR-106 osteoblastic cells. PTH 1-34, PTH 3-34, PTHrP and PTH 1-31 stimulated PKCα translocation and IL-6 promoter activity. Pharmacologic intervention at the adenylyl cyclase (AC) pathway (forskolin, IBMX, PKI) failed to alter PTH 1-34- or PTH 3-34-stimulated PKCα translocation. The phosphoinositol-phospholipase C (PI-PLC) antagonist U73122 slightly decreased PTH 1-34-stimulated PKCα translocation; however, the control analogue U73343 acted similarly. Propranolol, an inhibitor of phosphatidic acid (PA) phosphohydrolase, decreased diacylglycerol (DAG) formation and attenuated PTH 1-34- and PTH 3-34-stimulated PKCα translocation and IL-6 promoter activity, suggesting a phospholipase D (PLD)-dependent mechanism. This is the first demonstration that PLD-mediated signalling leads to both PKC-α translocation and IL-6 promoter activation in osteoblastic cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 105-114 |
| Number of pages | 10 |
| Journal | Cellular Signalling |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2004 |
Funding
The authors thank Dr. Bernd Stein for the IL-6 promoter construct and Dr. Zsolt Nagy for help with the luciferase assay. These studies were supported by Research Grant AR11262 to P.H. Stern from the National Institutes of Health. J.M. Radeff has received support from an Advanced Predoctoral Fellowship from the Pharmaceutical Research and Manufacturers of America Foundation and from the Chicago Baseball Charities Fellowship through the Robert H. Lurie Cancer Center.
Keywords
- Interleukin-6
- Osteoblast
- Parathyroid hormone
- Phospholipase D
- Protein kinase C isozymes
ASJC Scopus subject areas
- Cell Biology