Deubiquitinase USP17 Regulates Osteoblast Differentiation by Increasing Osterix Protein Stability

Deubiquitinases (DUBs) are essential for bone remodeling by regulating the differentiation of osteoblast and osteoclast. USP17 encodes for a deubiquitinating enzyme, specifically known as ubiquitin-specific protease 17, which plays a critical role in regulating protein stability and cellular signali...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-10, Vol.24 (20), p.15257
Main Authors: Kim, Myeong Ji, Piao, Meiyu, Li, Yuankuan, Lee, Sung Ho, Lee, Kwang Youl
Format: Article
Language:English
Subjects:
Bone diseases
Bone morphogenetic proteins
Cell cycle
deubiquitinase
Ethylenediaminetetraacetic acid
Fractures
Homeostasis
osteoblast differentiation
Osteoporosis
Osterix
Phosphatases
Proteases
Protein expression
Proteins
Signal transduction
Transcription factors
USP17
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Summary:Deubiquitinases (DUBs) are essential for bone remodeling by regulating the differentiation of osteoblast and osteoclast. USP17 encodes for a deubiquitinating enzyme, specifically known as ubiquitin-specific protease 17, which plays a critical role in regulating protein stability and cellular signaling pathways. However, the role of USP17 during osteoblast differentiation has not been elusive. In this study, we initially investigated whether USP17 could regulate the differentiation of osteoblasts. Moreover, USP17 overexpression experiments were conducted to assess the impact on osteoblast differentiation induced by bone morphogenetic protein 4 (BMP4). The positive effect was confirmed through alkaline phosphatase (ALP) expression and activity studies since ALP is a representative marker of osteoblast differentiation. To confirm this effect, Usp17 knockdown was performed, and its impact on BMP4-induced osteoblast differentiation was examined. As expected, knockdown of Usp17 led to the suppression of both ALP expression and activity. Mechanistically, it was observed that USP17 interacted with Osterix (Osx), which is a key transcription factor involved in osteoblast differentiation. Furthermore, overexpression of USP17 led to an increase in Osx protein levels. Thus, to investigate whether this effect was due to the intrinsic function of USP17 in deubiquitination, protein stabilization experiments and ubiquitination analysis were conducted. An increase in Osx protein levels was attributed to an enhancement in protein stabilization via USP17-mediated deubiquitination. In conclusion, USP17 participates in the deubiquitination of Osx, contributing to its protein stabilization, and ultimately promoting the differentiation of osteoblasts.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms242015257