title: Dentin Sialoprotein is a Novel Substrate of Matrix Metalloproteinase 9 in vitro and in vivo.
abstract: Dentin sialoprotein (DSP) is essential for dentinogenesis and processed into fragments in the odontoblast-like cells and the tooth compartments. Matrix metalloproteinase 9 (MMP9) is expressed in teeth from early embryonic to adult stage. Although MMP9 has been reported to be involved in some physiological and pathological conditions through processing substrates, its role in tooth development and whether DSP is a substrate of MMP9 remain unknown. In this study, the function of MMP9 in the tooth development was examined by observation of Mmp9 knockout (Mmp9-/-) mouse phenotype, and whether DSP is a substrate of MMP9 was explored by in vitro and in vivo experiments. The results showed that Mmp9-/- teeth displayed a phenotype similar to dentinogenesis imperfecta, including decreased dentin mineral density, abnormal dentin architecture, widened predentin and irregular predentin-dentin boundary. The distribution of MMP9 and DSP overlapped in the odontoblasts, the predentin, and the mineralized dentin, and MMP9 was able to specifically bind to DSP. MMP9 highly efficiently cleaved DSP into distinct fragments in vitro, and the deletion of Mmp9 caused improper processing of DSP in natural teeth. Therefore, our findings demonstrate that MMP9 is important for tooth development and DSP is a novel target of MMP9 during dentinogenesis.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology &Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.|Department of Developmental Dentistry, University of Texas Health Science Center, San Antonio, 78229, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Department of Developmental Dentistry, University of Texas Health Science Center, San Antonio, 78229, USA.|Department of Surgery, The First Affiliated Hospital, Fujian Medial University, Fuzhou, 350005, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Developmental Dentistry, University of Texas Health Science Center, San Antonio, 78229, USA.|Department of Anatomy and Histoembryology, Fujian Medical University, Fuzhou, 350018, China.
authors.forename: Junsheng
authors.initials: J
authors.lastname: Feng
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology &Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.|Department of Developmental Dentistry, University of Texas Health Science Center, San Antonio, 78229, USA.
authors.forename: Guobin
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Engineering, Mathematics and Physics, Texas A&M International University, Laredo, 78041, USA.
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Ni
authors.affiliation: Department of Periodontics, University of Texas Health Science Center, San Antonio, 78229, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology &Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.|Department of Developmental Dentistry, University of Texas Health Science Center, San Antonio, 78229, USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wan
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, 39216, USA.
authors.forename: Merry
authors.initials: M
authors.lastname: Lindsey
authors.affiliation: Department of Developmental Dentistry, University of Texas Health Science Center, San Antonio, 78229, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Donly
authors.affiliation: Department of Oral/Maxillofacial Surgery/Institute of Oral Health Research, University of Alabama at Birmingham School of Dentistry, Birmingham, 35294, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: MacDougall
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology &Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Developmental Dentistry, University of Texas Health Science Center, San Antonio, 78229, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D003804:Dentin / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D003810:Dentinogenesis; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009804:Odontoblasts / Q000166:cytology / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D012795:Sialoglycoproteins / Q000378:metabolism*; D013379:Substrate Specificity; D000099311:Dentin Sialophosphoprotein
chemical_list: D016326:Extracellular Matrix Proteins; D020780:Matrix Metalloproteinase 9; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein