Role of special AT-rich sequence-binding protein 2 in the osteogenesis of dental mesenchymal stem cells.

Dental mesenchymal stem cells are recognized as a critical factor in repair of defective craniofacial bone owing to the multiple differentiation potential, the ability to regenerate distinct tissues, and the advantage that they can be easily obtained by relatively non-invasive procedures. Special AT-rich sequence-binding protein 2(SATB2)is a nuclear matrix protein, involved in chromatin remodeling and transcriptional regulation, and has been reported to be as a positive regulator of osteoblast differentiation, bone formation, and bone regeneration in mesenchymal stem cells. Here, we systematically investigated the capability of SATB2 to promote the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs), and stem cells from human exfoliated deciduous teeth (SHED). RNA-seq analysis and quantitative RT-PCR revealed that genes regulating osteogenic differentiation were differentially expressed among three cell types and SATB2 was found to be expressed at a relatively high level. When the three cell types were overexpressed SATB2 with AdSATB2 infection, ALP staining, ALP activity, Alizarin Red S staining and quantification tended to increase with an increasing infection rate. It showed opposite results after infection with AdsiSATB2. RNA-seq analysis indicated that the expression of downstream osteogenic genes was affected by AdSATB2 infection and quantitative RT-PCR confirmed that nine osteogenic genes (Spp1, Sema7a, Atf4, Ibsp, Col1a1, Sp7, Igfbp3, Dlx3, and Alpl) were upregulated, to various extents, following SATB2 overexpression. In addition, qPCR results indicated that SATB2 affected the expression of mesenchymal stem cell markers. These results suggested an important role of SATB2 in the osteogenesis of PDLSCs, DPSCs, and SHED. Further research is warranted to investigate SATB2-mediated regulation of osteogenic differentiation and to evaluate the therapeutic use of SATB2 for the regeneration of defective craniofacial bone tissue.

[1]  Zhengzhao Li,et al.  Cordycepin promotes osteogenesis of bone marrow-derived mesenchymal stem cells and accelerates fracture healing via hypoxia in a rat model of closed femur fracture. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[2]  F. Lundy,et al.  A Comparative Analysis of the Osteogenic Potential of Dental Mesenchymal Stem Cells. , 2019, Stem cells and development.

[3]  P. Pastore,et al.  Bioactive Sphene-Based Ceramic Coatings on cpTi Substrates for Dental Implants: An In Vitro Study , 2018, Materials.

[4]  J. Batista,et al.  Influence of Platelet-Poor Plasma on Angiogenesis and Maintenance of Volume in Autogenous Bone Grafts. , 2018, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[5]  K. Tanimoto,et al.  Comparative characterization of stem cells from human exfoliated deciduous teeth, dental pulp, and bone marrow-derived mesenchymal stem cells. , 2018, Biochemical and biophysical research communications.

[6]  R. Bloomquist,et al.  A quiescent cell population replenishes mesenchymal stem cells to drive accelerated growth in mouse incisors , 2018, Nature Communications.

[7]  Jiake Xu,et al.  TNF-α inhibits SATB2 expression and osteoblast differentiation through NF-κB and MAPK pathways , 2017, Oncotarget.

[8]  B. Meenan,et al.  Osteoblastic differentiation of periodontal ligament stem cells on non-stoichiometric calcium phosphate and titanium surfaces. , 2017, Journal of biomedical materials research. Part A.

[9]  P. Sharpe Dental mesenchymal stem cells , 2016, Development.

[10]  M. Ding,et al.  Assessment of activated porous granules on implant fixation and early bone formation in sheep , 2015, Journal of orthopaedic translation.

[11]  P. T. Sharpe,et al.  Composition of Mineral Produced by Dental Mesenchymal Stem Cells , 2015, Journal of dental research.

[12]  S. Tran,et al.  Osteogenic Potential of Dental Mesenchymal Stem Cells in Preclinical Studies: A Systematic Review Using Modified ARRIVE and CONSORT Guidelines , 2015, Stem cells international.

[13]  Hongchen Liu,et al.  Regulative Effect of Mir-205 on Osteogenic Differentiation of Bone Mesenchymal Stem Cells (BMSCs): Possible Role of SATB2/Runx2 and ERK/MAPK Pathway , 2015, International journal of molecular sciences.

[14]  T. He,et al.  A Simplified and Versatile System for the Simultaneous Expression of Multiple siRNAs in Mammalian Cells Using Gibson DNA Assembly , 2014, PloS one.

[15]  T. He,et al.  Bone morphogenetic protein 2 inhibits the proliferation and growth of human colorectal cancer cells , 2014, Oncology reports.

[16]  Huijun Wang,et al.  Lentiviral-mediated expression of SATB2 promotes osteogenic differentiation of bone marrow stromal cells in vitro and in vivo. , 2014, European journal of oral sciences.

[17]  X. Chen,et al.  Overexpression of Ad5 precursor terminal protein accelerates recombinant adenovirus packaging and amplification in HEK-293 packaging cells , 2014, Gene Therapy.

[18]  T. He,et al.  Adenovirus-Mediated Gene Transfer in Mesenchymal Stem Cells Can Be Significantly Enhanced by the Cationic Polymer Polybrene , 2014, PloS one.

[19]  Jiake Xu,et al.  The role of SATB2 in skeletogenesis and human disease. , 2014, Cytokine & growth factor reviews.

[20]  T. He,et al.  The E-F Hand Calcium-Binding Protein S100A4 Regulates the Proliferation, Survival and Differentiation Potential of Human Osteosarcoma Cells , 2013, Cellular Physiology and Biochemistry.

[21]  Ning Leng,et al.  EBSeq: an empirical Bayes hierarchical model for inference in RNA-seq experiments , 2013, Bioinform..

[22]  Young Guk Park,et al.  Special AT-rich sequence-binding protein 2 and its related genes play key roles in the differentiation of MC3T3-E1 osteoblast like cells. , 2012, Biochemical and biophysical research communications.

[23]  Min Seok Kim,et al.  Roles of SATB2 in osteogenic differentiation and bone regeneration. , 2011, Tissue engineering. Part A.

[24]  T. He,et al.  Retinoic Acids Potentiate BMP9-Induced Osteogenic Differentiation of Mesenchymal Progenitor Cells , 2010, PloS one.

[25]  Cole Trapnell,et al.  Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. , 2010, Nature biotechnology.

[26]  F. García-Godoy,et al.  Osteogenic differentiation of stem cells derived from human periodontal ligaments and pulp of human exfoliated deciduous teeth , 2010, Cell and Tissue Research.

[27]  T. He,et al.  BMP‐9‐induced osteogenic differentiation of mesenchymal progenitors requires functional canonical Wnt/β‐catenin signalling , 2009, Journal of cellular and molecular medicine.

[28]  T. He,et al.  A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells. , 2009, Stem cells and development.

[29]  C. McCulloch Origins and functions of cells essential for periodontal repair: the role of fibroblasts in tissue homeostasis. , 2008, Oral diseases.

[30]  V. Tarabykin,et al.  SATB2 interacts with chromatin‐remodeling molecules in differentiating cortical neurons , 2008, The European journal of neuroscience.

[31]  G. Schmalz,et al.  Somatic stem cells for regenerative dentistry , 2008, Clinical Oral Investigations.

[32]  Paolo Giannoni,et al.  A tissue engineering approach to bone repair in large animal models and in clinical practice. , 2007, Biomaterials.

[33]  K. Kinzler,et al.  A protocol for rapid generation of recombinant adenoviruses using the AdEasy system , 2007, Nature Protocols.

[34]  R. Krumlauf,et al.  Bone Formation: The Nuclear Matrix Reloaded , 2006, Cell.

[35]  I. Fariñas,et al.  SATB2 Is a Multifunctional Determinant of Craniofacial Patterning and Osteoblast Differentiation , 2006, Cell.

[36]  C. Paweletz,et al.  Isolation and Characterization of SATB2, a Novel AT-rich DNA Binding Protein Expressed in Development- and Cell-Specific Manner in the Rat Brain , 2006, Neurochemical Research.

[37]  D. Murphy,et al.  Role of the Redox Protein Thioredoxin in Cytoprotective Mechanism Evoked by (-)-Deprenyl , 2005, Molecular Pharmacology.

[38]  Eleftherios Tsiridis,et al.  Bone substitutes: an update. , 2005, Injury.

[39]  O. Britanova,et al.  Novel transcription factor Satb2 interacts with matrix attachment region DNA elements in a tissue‐specific manner and demonstrates cell‐type‐dependent expression in the developing mouse CNS , 2005, The European journal of neuroscience.

[40]  J. Szatkowski,et al.  Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery , 2004, Gene Therapy.

[41]  P. Sharpe,et al.  Neural crest contribution to mammalian tooth formation. , 2004, Birth defects research. Part C, Embryo today : reviews.

[42]  R. Grosschedl,et al.  SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression. , 2003, Genes & development.

[43]  J. Szatkowski,et al.  Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs) 1 1 J Bone Joint Surg Am 2003;85A:1544–52 , 2003 .

[44]  Stan Gronthos,et al.  SHED: Stem cells from human exfoliated deciduous teeth , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[45]  S. Gronthos,et al.  Perivascular Niche of Postnatal Mesenchymal Stem Cells in Human Bone Marrow and Dental Pulp , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[46]  S. Gronthos,et al.  Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[47]  I. About,et al.  Human dentin production in vitro. , 2000, Experimental cell research.

[48]  G. R. Imm,et al.  A Comparative Study of Human Periodontal Ligament Cells and Gingival Fibroblasts in vitro , 1988, Journal of dental research.

[49]  T. He,et al.  Canonical Wnt signaling acts synergistically on BMP9-induced osteo/odontoblastic differentiation of stem cells of dental apical papilla (SCAPs). , 2015, Biomaterials.

[50]  I. Thesleff,et al.  Tissue Interactions Regulating Tooth Development and Renewal. , 2015, Current topics in developmental biology.