Characterization of Runx2 phosphorylation sites required for TGF-β1-mediated stimulation of matrix metalloproteinase-13 expression in osteoblastic cells

2017 ◽  
Vol 233 (2) ◽  
pp. 1082-1094 ◽  
Author(s):  
Balasubramanian Arumugam ◽  
Mariappanadar Vairamani ◽  
Nicola C. Partridge ◽  
Nagarajan Selvamurugan
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Kanagaraj Gomathi ◽  
Muthukumar Rohini ◽  
Nicola C. Partridge ◽  
Nagarajan Selvamurugan

Abstract Transforming growth factor beta 1 (TGF-β1) functions as a coupling factor between bone development and resorption. Matrix metalloproteinase 13 (MMP13) is important in bone remodeling, and skeletal dysplasia is caused by a deficiency in MMP13 expre-ssion. Runx2, a transcription factor is essential for bone development, and MMP13 is one of its target genes. TGF-β1 promoted Runx2 phosphorylation, which was necessary for MMP13 production in osteoblastic cells, as we previously shown. Since the phosphorylation of some proteins causes them to be degraded by the ubiquitin/proteasome pathway, we hypothesized that TGF-β1 might stabilize the phosphorylated Runx2 protein for its activity by other post-translational modification (PTM). This study demonstrated that TGF-β1-stimulated Runx2 acetylation in rat osteoblastic cells. p300, a histone acetyltransferase interacted with Runx2, and it promoted Runx2 acetylation upon TGF-β1-treatment in these cells. Knockdown of p300 decreased the TGF-β1-stimulated Runx2 acetylation and MMP13 expression in rat osteoblastic cells. TGF-β1-treatment stimulated the acetylated Runx2 bound at the MMP13 promoter, and knockdown of p300 reduced this effect in these cells. Overall, our studies identified the transcriptional regulation of MMP13 by TGF-β1 via Runx2 acetylation in rat osteoblastic cells, and these findings contribute to the knowledge of events presiding bone metabolism.


2007 ◽  
Vol 17 (1) ◽  
pp. 66-71 ◽  
Author(s):  
L. T. Gooljarsingh ◽  
A. Lakdawala ◽  
F. Coppo ◽  
L. Luo ◽  
G. B. Fields ◽  
...  

2014 ◽  
Vol 57 (22) ◽  
pp. 9598-9611 ◽  
Author(s):  
Timothy P. Spicer ◽  
Jianwen Jiang ◽  
Alexander B. Taylor ◽  
Jun Yong Choi ◽  
P. John Hart ◽  
...  

2005 ◽  
Vol 98 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Kiyoshi Migita ◽  
Taichiro Miyashita ◽  
Yumi Maeda ◽  
Takahiko Aoyagi ◽  
Yojiro Kawabe ◽  
...  

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