Increased expression of G11α in osteoblastic cells enhances parathyroid hormone activation of phospholipase C and AP-1 regulation of matrix metalloproteinase-13 mRNA

✍ Scribed by Ricky Cheung; Mary S. Erclik; Jane Mitchell

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 337 KB
• Volume: 204
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20299

✦ Synopsis

Abstract

In osteoblasts parathyroid hormone (PTH) stimulates the PTH/PTH‐related peptide (PTHrP) receptor (PTH1R) that couples via G~s~ to adenylyl cyclase stimulation and via G~11~ to phospholipase C (PLC) stimulation. We have investigated the effect of increasing G~11~α levels in UMR 106‐01 osteoblastic cells by transient transfection with cDNA encoding G~11~α on PTH stimulation of PLC and protein kinase C (PKC) as well as PTH regulation of mRNA encoding matrix metalloproteinase‐13 (MMP‐13). Transfection with G~11~α cDNA resulted in a 5‐fold increase in PTH‐stimulated PLC activity with no change in PTH‐stimulated adenylyl cyclase. PTH‐induced translocation of PKC‐βI, ‐δ, and ‐ζ to the cell membrane and PKC‐ζ to the nucleus was also increased. Increased G~11~α protein resulted in increased stimulation of MMP‐13 mRNA levels at all doses of PTH. There was a 2.5 ± 0.35 fold increase in maximal PTH‐stimulation of c‐jun mRNA and smaller but significant increases in c‐fos accompanied by increased basal and PTH‐stimulated AP‐1 binding in cells expressing increased G~11~α. Runx‐2 mRNA and protein levels were not significantly increased by increased G~11~α expression. The increase in PTH stimulation of c‐jun, c‐fos, and MMP‐13 in G~11~α‐transfected cells were all blocked by bisindolylmaleimide I, a selective inhibitor of PKC. These results demonstrate that regulation of the PLC pathway through the PTH1R is significantly increased by elevating expression of G~11~α in osteoblastic cells. This leads to increased PTH stimulation of MMP‐13 expression by increased stimulation of AP‐1 factors c‐jun and c‐fos. © 2005 Wiley‐Liss, Inc.