TGFβ1 suppressed matrix mineralization of osteoblasts differentiation by regulating SMURF1–C/EBPβ–DKK1 axisopen access
- Authors
- Nam, Bora; Park, Hyosun; Lee, Young Lim; Oh, Younseo; Park, Jinsung; Kim, So Yeon; Weon, Subin; Choi, Sung Hoon; Yang, Jae-Hyuk; Jo, Sungsin; Kim, Tae-Hwan
- Issue Date
- Dec-2020
- Publisher
- MDPI
- Keywords
- osteoblast differentiation; mineralization; TGF beta 1; SMURF1; C/EBP beta; DKK1
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.21, no.24, pp.1 - 15
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 21
- Number
- 24
- Start Page
- 1
- End Page
- 15
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/8192
- DOI
- 10.3390/ijms21249771
- ISSN
- 1661-6596
- Abstract
- Transforming growth factor β1 (TGFβ1) is a major mediator in the modulation of osteoblast differentiation. However, the underlying molecular mechanism is still not fully understood. Here, we show that TGFβ1 has a dual stage-dependent role in osteoblast differentiation; TGFβ1 induced matrix maturation but inhibited matrix mineralization. We discovered the underlying mechanism of the TGFβ1 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/EBPβ) were dramatically suppressed by TGFβ1 treatment. The suppressive effects of TGFβ1 were reversed with anti-TGFβ1 treatment. Mechanically, TGFβ1 decreased protein levels of C/EBPβ without changing mRNA levels and reduced both mRNA and protein levels of DKK1. The degradation of the C/EBPβ protein by TGFβ1 was dependent on the ubiquitin–proteasome pathway. TGFβ1 degraded the C/EBPβ protein by inducing the expression of the E3 ubiquitin ligase Smad ubiquitin regulatory factor 1 (SMURF1) at the transcript level, thereby reducing the C/EBPβ-DKK1 regulatory mechanism. Collectively, our findings suggest that TGFβ1 suppressed the matrix mineralization of osteoblast differentiation by regulating the SMURF1-C/EBPβ-DKK1 axis.
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