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Ubiquitin‐specific protease USP 34 controls osteogenic differentiation and bone formation by regulating BMP 2 signaling
Author(s) -
Guo Yuchen,
Wang Mengyuan,
Zhang Shiwen,
Wu Yunshu,
Zhou Chenchen,
Zheng Rixin,
Shao Bin,
Wang Yuan,
Xie Liang,
Liu Weiqing,
Sun Ningyuan,
Jing Junjun,
Ye Ling,
Chen Qianming,
Yuan Quan
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899398
Subject(s) - biology , bone morphogenetic protein 2 , microbiology and biotechnology , protease , bone morphogenetic protein , ubiquitin , signal transduction , biochemistry , enzyme , in vitro , gene
Abstract The osteogenic differentiation of mesenchymal stem cells ( MSC s) is governed by multiple mechanisms. Growing evidence indicates that ubiquitin‐dependent protein degradation is critical for the differentiation of MSC s and bone formation; however, the function of ubiquitin‐specific proteases, the largest subfamily of deubiquitylases, remains unclear. Here, we identify USP 34 as a previously unknown regulator of osteogenesis. The expression of USP 34 in human MSC s increases after osteogenic induction while depletion of USP 34 inhibits osteogenic differentiation. Conditional knockout of Usp34 from MSC s or pre‐osteoblasts leads to low bone mass in mice. Deletion of Usp34 also blunts BMP 2‐induced responses and impairs bone regeneration. Mechanically, we demonstrate that USP 34 stabilizes both Smad1 and RUNX 2 and that depletion of Smurf1 restores the osteogenic potential of Usp34‐deficient MSC s in vitro . Taken together, our data indicate that USP 34 is required for osteogenic differentiation and bone formation.