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Increased expression of G 11 α in osteoblastic cells enhances parathyroid hormone activation of phospholipase C and AP‐1 regulation of matrix metalloproteinase‐13 mRNA
Author(s) -
Cheung Ricky,
Erclik Mary S.,
Mitchell Jane
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20299
Subject(s) - protein kinase c , parathyroid hormone , medicine , endocrinology , adenylyl cyclase , phospholipase c , stimulation , transfection , signal transduction , chemistry , receptor , microbiology and biotechnology , biology , cell culture , calcium , genetics
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.