title: Depletion of MEIS2 inhibits osteogenic differentiation potential of human dental stem cells.
abstract: Dental mesenchymal stem cells (MSCs) are a reliable and promising cell source for the regeneration of tooth,bone and other tissues . However, the molecular mechanisms underlying their differentiation are still largely unknown, which restricts their further wide application. Here, we investigate regulatory function of homeobox gene MEIS2 in the osteogenic differentiation potential of MSCs using stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) by loss-of-function experiments. Our findings demonstrated that knockdown of MEIS2 in SCAPs and DPSCs decreased alkaline phosphatase (ALP) activity and mineralization, and inhibited the mRNA expression of ALP, bone sialoprotein (BSP), and osteocalcin (OCN). Besides, depletion of MEIS2 resulted in reduced expression of the key osteogenesis-related transcription factor, osterix (OSX) but not in the expression of runt-related transcription factor 2 (RUNX2). Furthermore, MEIS2 expression significantly increased during osteogenic induction and was strongly upregulated by BMP4 stimulation. Taken together, these results indicated that MEIS2 played an essential role in maintaining osteogenic differentiation potential of dental tissue- derived MSCs. These findings will provide new insights into the mechanisms underlying directed differentiation of MSCs, and identify a potential target gene in dental tissues derived MSCs for promoting the tissue regeneration.
authors.affiliation: Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China ; Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology Beijing 100050, China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology Beijing 100050, China ; Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences Beijing 100069, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Dong
authors.affiliation: Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Endodontics, Tianjin Medical University School of Stomatology Tianjin 300070, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology Beijing 100050, China ; Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences Beijing 100069, China.
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
keywords: MEIS2; Mesenchymal stem cell; homeobox gene; osteogenic differentiation; tooth