TGF beta 1 Suppressed Matrix Mineralization of Osteoblasts Differentiation by Regulating SMURF1-C/EBP beta-DKK1 Axis
- Title
- TGF beta 1 Suppressed Matrix Mineralization of Osteoblasts Differentiation by Regulating SMURF1-C/EBP beta-DKK1 Axis
- Author
- 양재혁
- Keywords
- osteoblast differentiation; mineralization; TGFβ1; SMURF1; C/EBPβ; DKK1
- Issue Date
- 2020-12
- Publisher
- MDPI
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, no. 24, article no. 9771, page. 1-15
- Abstract
- Transforming growth factor beta 1 (TGF beta 1) is a major mediator in the modulation of osteoblast differentiation. However, the underlying molecular mechanism is still not fully understood. Here, we show that TGF beta 1 has a dual stage-dependent role in osteoblast differentiation; TGF beta 1 induced matrix maturation but inhibited matrix mineralization. We discovered the underlying mechanism of the TGF beta 1 inhibitory role in mineralization using human osteoprogenitors. In particular, the matrix mineralization-related genes of osteoblasts such as osteocalcin (OCN), Dickkopf 1 (DKK1), and CCAAT/enhancer-binding protein beta (C/EBP beta) were dramatically suppressed by TGF beta 1 treatment. The suppressive effects of TGF beta 1 were reversed with anti-TGF beta 1 treatment. Mechanically, TGF beta 1 decreased protein levels of C/EBP beta without changing mRNA levels and reduced both mRNA and protein levels of DKK1. The degradation of the C/EBP beta protein by TGF beta 1 was dependent on the ubiquitin-proteasome pathway. TGF beta 1 degraded the C/EBP beta protein by inducing the expression of the E3 ubiquitin ligase Smad ubiquitin regulatory factor 1 (SMURF1) at the transcript level, thereby reducing the C/EBP beta-DKK1 regulatory mechanism. Collectively, our findings suggest that TGF beta 1 suppressed the matrix mineralization of osteoblast differentiation by regulating the SMURF1-C/EBP beta-DKK1 axis.
- URI
- https://www.mdpi.com/1422-0067/21/24/9771https://repository.hanyang.ac.kr/handle/20.500.11754/174989
- ISSN
- 1422-0067; 1661-6596
- DOI
- 10.3390/ijms21249771
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
- Files in This Item:
- TGFβ1 Suppressed Matrix Mineralization of Osteoblasts Differentiation by Regulating SMURF1-CEBPβ-DKK1 Axis.pdfDownload
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