Ubiquitin-specific protease USP34 controls osteogenic differentiation and bone formation by regulating BMP2 signaling.
The osteogenic differentiation of mesenchymal stem cells (MSCs) is governed by multiple mechanisms. Growing evidence indicates that ubiquitin-dependent protein degradation is critical for the differentiation of MSCs and bone formation; however, the function of ubiquitin-specific proteases, the largest subfamily of deubiquitylases, remains unclear. Here, we identify USP34 as a previously unknown regulator of osteogenesis. The expression of USP34 in human MSCs increases after osteogenic induction while depletion of USP34 inhibits osteogenic differentiation. Conditional knockout of Usp34 from MSCs or pre-osteoblasts leads to low bone mass in mice. Deletion of Usp34 also blunts BMP2-induced responses and impairs bone regeneration. Mechanically, we demonstrate that USP34 stabilizes both Smad1 and RUNX2 and that depletion of Smurf1 restores the osteogenic potential of Usp34-deficient MSCs in vitro Taken together, our data indicate that USP34 is required for osteogenic differentiation and bone formation.
Authors: Guo YC1, Wang MY1, Zhang SW1, Wu YS1, Zhou CC1, Zheng RX1, Shao B1, Wang Y1, Xie L1, Liu WQ1, Sun NY1, Jing JJ1, Ye L1, Chen QM1, Yuan Q2.
Influence Factor: 10.56
Citation: EMBO J 37, (2018).