Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2
- 주제(키워드) cyclophilin A , osteoblast , Runx2 , Akt signaling
- 주제(기타) Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
- 설명문(일반) [Piao, Meiyu; Kim, Myeong Ji] Chonnam Natl Univ, Coll Pharm, Gwangju 61186, South Korea; [Lee, Sung Ho; Lee, Kwang Youl] Chonnam Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, Gwangju 61186, South Korea; [Choi, Joong-Kook] Chungbuk Natl Univ, Div Biochem, Coll Med, Cheongju 28644, South Korea; [Yeo, Chang-Yeol] Ewha Womans Univ, Dept Life Sci, Res Ctr Cellular Homeostasis, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 MDPI
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000202945
- 본문언어 영어
- Published As https://doi.org/10.3390/ijms23169244
- PubMed https://pubmed.ncbi.nlm.nih.gov/36012517
초록/요약
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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