当前位置： SCI文献检索 > EXPERIMENTAL CELL RESEARCH期刊下所有文献 > Parathyroid hormone-related peptide (PTHrP) inhibits Runx2 expression through the PKA signaling pathway.

Parathyroid hormone-related peptide (PTHrP) inhibits Runx2 expression through the PKA signaling pathway.

Abstract：

:The bone-related transcription factor Runx2 (Cbfa1) has been extensively shown to regulate osteoblast differentiation and function. Recent studies demonstrate that Runx2 is also a positive regulator of chondrocyte maturation and vascular invasion in cartilage. Runx2 activity can be modulated in several ways, including direct stimulation of gene expression, post-translational modification, and protein-protein interactions. We have previously reported cooperative effects between BMP and RA downstream signaling involving Smad proteins and Runx2. Furthermore, our previous studies showed that PTHrP inhibits chondrocyte maturation primarily through CREB and AP-1 signaling pathways. In the present study, we investigated the effect of PTHrP on Runx2 expression in chick upper sternal chondrocytes (USCs). We further determined the signaling pathways through which PTHrP regulates Runx2 transcription. Our results show that PTHrP inhibits Runx2 expression at both the mRNA and protein levels concomitant with a PTHrP-mediated suppression of the phenotypic marker of hypertrophy, type X collagen. We further determined potential signaling pathways through which PTHrP inhibits Runx2 expression using protein kinase inhibitors, H89 (PKA inhibitor): Go-6976 (PKC inhibitor): SB203850 (p38 MAPK inhibitor), and U0126 (MEK inhibitor). We show that pretreatment with PKA and, to a lesser extent, PKC inhibitors significantly blocked PTHrP suppression of Runx2, while p38 MAPK and MEK inhibitors had no significant effect. Furthermore, PTHrP suppression of Runx2 mRNA was partially blocked in USCs infected with RCAS-A-CREB, a dominant negative reagent that abrogates CREB activity. Overall, our results demonstrate that PTHrP downregulates Runx2 expression primarily through the PKA signaling pathway.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Li TF,Dong Y,Ionescu AM,Rosier RN,Zuscik MJ,Schwarz EM,O'Keefe RJ,Drissi H

doi

10.1016/j.yexcr.2004.05.025

keywords:

subject

Has Abstract

pub_date

2004-09-10 00:00:00

pages

128-36

issue

eissn

0014-4827

issn

1090-2422

pii

S0014482704003015

journal_volume

299

pub_type

杂志文章

在线工具

Parathyroid hormone-related peptide (PTHrP) inhibits Runx2 expression through the PKA signaling pathway.