title: Shh signaling, negatively regulated by BMP signaling, inhibits the osteo/dentinogenic differentiation potentials of mesenchymal stem cells from apical papilla.
abstract: Mesenchymal stem cells (MSCs) derived from dental tissues show promise for use in tooth-related tissue regeneration, but the molecular mechanisms underlying their directed differentiation remain unclear, limiting their usefulness. Sonic Hedgehog (Shh) signaling is a major signaling pathway that regulates cell differentiation and osteogenesis. We found that when Shh signaling was activated by human recombinant SHH-N protein or by overexpression of active mutant M2-Smoothened (SMO) in stem cells from apical papilla (SCAPs), GLI1, a key downstream transcription factor and a marker of Shh signaling, was upregulated. Subsequently, in vitro osteo/dentinogenic differentiation and in vivo osteogenesis were inhibited in SCAPs. Moreover, the expression of GLI1 and SMO were downregulated by BMP signaling while osteo/dentinogenic differentiation in SCAPs was upregulated. These results provide insights into the role of Shh signaling in the directed differentiation of MSCs derived from dental tissues and suggest possible target genes for optimizing the use of stem cells of dental origin for tissue regeneration applications.
authors.affiliation: Laboratory of Molecular Signaling and Stem Cells Therapy, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tiantan Xili No.4, Dongcheng District, Beijing, 100050, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Jiang
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Yin
authors.forename: Zhaochen
authors.initials: Z
authors.lastname: Shan
authors.forename: Yushi
authors.initials: Y
authors.lastname: Ma
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Fan
mesh_terms: D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D003771:Dental Papilla / Q000166:cytology*; D003810:Dentinogenesis / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D050505:Mutant Proteins / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: D019485:Bone Morphogenetic Proteins; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D050505:Mutant Proteins; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000469:Alkaline Phosphatase