DUSP5 promotes osteogenic differentiation through SCP1/2 ‐dependent phosphorylation of SMAD1

DUSP5 promotes the osteogenic differentiation of MSCs by repressing SMAD1 signaling pathway in a SCP1/2 dependent manner. The linker region of DUSP5 occupies the phosphatase domain of SCP1/2 and thereby releases the inhibitory effect of SCP1/2 on SMAD1 signaling. Additionally,Dusp5 overexpression could effectively ameliorate osteopenia of mice. AbstractDual-specificity phosphatases (DUSPs) are defined by their capability to dephosphorylates both phosphoserine/phosphothreonine (pSer/pThr) and phosphotyrosine (pTyr). DUSP5, a member of DUSPs superfamily, is located in the nucleus and plays crucially regulatory role in the signaling pathway transduction. In our present study, we discover that DUSP5 significantly promotes osteogenic differentiation of MSCs by activating SMAD1 signaling pathway. Mechanistically, DUSP5 physically interacts with the phosphatase domain of small C-terminal phosphatase 1/2 (SCP1/2, SMAD1 phosphatases) by the linker region. And we further confirm that DUSP5 activates SMAD1 signaling through a SCP1/2 dependent manner. Specifically, DUSP5 attenuates the SCP1/2-SMAD1 interaction by competitively binding to SCP1/2, which is responsible for the SMAD1 dephosphorylation, and thus resulted in the activation of SMAD1 signaling. Importantly, DUSP5 expression in mouse bone marrow mesenchymal stromal cells (mBMMSCs) was significantly reduced in ovariectomized (OVX) mice in which osteogenesis was highly passive, and overexpression ofDusp5 via tail vein injection rev...

Source: Stem Cells - June 25, 2021 Category: Stem Cells Authors: Xuejiao Liu, Xuenan Liu, Yangge Du, Menglong Hu, Yueming Tian, Zheng Li, Longwei Lv, Xiao Zhang, Yunsong Liu, Yongsheng Zhou, Ping Zhang Tags: Tissue ‐Specific Stem Cells Source Type: research