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Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2

Cyclophilin A (CypA) is a ubiquitously expressed and highly conserved protein with peptidyl-prolyl cis-trans isomerase activity that is involved in various biological activities by regulating protein folding and trafficking. Although CypA has been reported to positively regulate osteoblast different...

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Autores principales: Piao, Meiyu, Lee, Sung Ho, Kim, Myeong Ji, Choi, Joong-Kook, Yeo, Chang-Yeol, Lee, Kwang Youl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409320/
https://www.ncbi.nlm.nih.gov/pubmed/36012517
http://dx.doi.org/10.3390/ijms23169244
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author Piao, Meiyu
Lee, Sung Ho
Kim, Myeong Ji
Choi, Joong-Kook
Yeo, Chang-Yeol
Lee, Kwang Youl
author_facet Piao, Meiyu
Lee, Sung Ho
Kim, Myeong Ji
Choi, Joong-Kook
Yeo, Chang-Yeol
Lee, Kwang Youl
author_sort Piao, Meiyu
collection PubMed
description Cyclophilin A (CypA) is a ubiquitously expressed and highly conserved protein with peptidyl-prolyl cis-trans isomerase activity that is involved in various biological activities by regulating protein folding and trafficking. Although CypA has been reported to positively regulate osteoblast differentiation, the mechanistic details remain largely unknown. In this study, we aimed to elucidate the mechanism of CypA-mediated regulation of osteoblast differentiation. Overexpression of CypA promoted osteoblast differentiation in bone morphogenic protein 4 (BMP4)-treated C2C12 cells, while knockdown of CypA inhibited osteoblast differentiation in BMP4-treated C2C12. CypA and Runx2 were shown to interact based on immunoprecipitation experiments and CypA increased Runx2 transcriptional activity in a dose-dependent manner. Our results indicate that this may be because CypA can increase the DNA binding affinity of Runx2 to Runx2 binding sites such as osteoblast-specific cis-acting element 2. Furthermore, to identify factors upstream of CypA in the regulation of osteoblast differentiation, various kinase inhibitors known to affect osteoblast differentiation were applied during osteogenesis. Akt inhibition resulted in the most significant suppression of osteogenesis in BMP4-induced C2C12 cells overexpressing CypA. Taken together, our results show that CypA positively regulates osteoblast differentiation by increasing the DNA binding affinity of Runx2, and Akt signaling is upstream of CypA.
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spelling pubmed-94093202022-08-26 Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2 Piao, Meiyu Lee, Sung Ho Kim, Myeong Ji Choi, Joong-Kook Yeo, Chang-Yeol Lee, Kwang Youl Int J Mol Sci Article Cyclophilin A (CypA) is a ubiquitously expressed and highly conserved protein with peptidyl-prolyl cis-trans isomerase activity that is involved in various biological activities by regulating protein folding and trafficking. Although CypA has been reported to positively regulate osteoblast differentiation, the mechanistic details remain largely unknown. In this study, we aimed to elucidate the mechanism of CypA-mediated regulation of osteoblast differentiation. Overexpression of CypA promoted osteoblast differentiation in bone morphogenic protein 4 (BMP4)-treated C2C12 cells, while knockdown of CypA inhibited osteoblast differentiation in BMP4-treated C2C12. CypA and Runx2 were shown to interact based on immunoprecipitation experiments and CypA increased Runx2 transcriptional activity in a dose-dependent manner. Our results indicate that this may be because CypA can increase the DNA binding affinity of Runx2 to Runx2 binding sites such as osteoblast-specific cis-acting element 2. Furthermore, to identify factors upstream of CypA in the regulation of osteoblast differentiation, various kinase inhibitors known to affect osteoblast differentiation were applied during osteogenesis. Akt inhibition resulted in the most significant suppression of osteogenesis in BMP4-induced C2C12 cells overexpressing CypA. Taken together, our results show that CypA positively regulates osteoblast differentiation by increasing the DNA binding affinity of Runx2, and Akt signaling is upstream of CypA. MDPI 2022-08-17 /pmc/articles/PMC9409320/ /pubmed/36012517 http://dx.doi.org/10.3390/ijms23169244 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Piao, Meiyu
Lee, Sung Ho
Kim, Myeong Ji
Choi, Joong-Kook
Yeo, Chang-Yeol
Lee, Kwang Youl
Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2
title Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2
title_full Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2
title_fullStr Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2
title_full_unstemmed Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2
title_short Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2
title_sort cyclophilin a promotes osteoblast differentiation by regulating runx2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409320/
https://www.ncbi.nlm.nih.gov/pubmed/36012517
http://dx.doi.org/10.3390/ijms23169244
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