TY - JOUR
T1 - Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells
AU - Gomathi, Kanagaraj
AU - Rohini, Muthukumar
AU - Partridge, Nicola C.
AU - Selvamurugan, Nagarajan
N1 - Funding Information:
Research funding: A grant from India’s Department of Science and Technology-Science and Engineering Research Board (DST-SERB) sponsored this research (CRG/2018/000051 to N.S.).
Publisher Copyright:
© 2021 Walter de Gruyter GmbH, Berlin/Boston.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - Runx2
KW - acetylation
KW - matrix metalloproteinase 13 (MMP13)
KW - transforming growth factor beta 1 (TGF-β1)
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U2 - 10.1515/hsz-2021-0292
DO - 10.1515/hsz-2021-0292
M3 - Article
C2 - 34643076
AN - SCOPUS:85117473332
SN - 1431-6730
VL - 403
SP - 305
EP - 315
JO - Biological Chemistry
JF - Biological Chemistry
IS - 3
ER -