title: Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice.
abstract: FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). While the assumed phosphorylation failure of the SIBLINGs is likely associated with the defects in the Fam20C-deficient mice, it remains unclear if the downregulation of Dmp1 contributes to these phenotypes. In this study, we crossed 3.6 kb Col1-Dmp1 transgenic mice with 3.6 kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. These results indicated that the downregulation of Dmp1 may not directly associate with, or significantly contribute to the bone and dentin defects in the Fam20C-cKO mice.
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry , Dallas, TX , USA and.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.forename: Jingya
authors.initials: J
authors.lastname: Wang
authors.forename: Baozhi
authors.initials: B
authors.lastname: Yuan
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Lu
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
authors.forename: Chunlin
authors.initials: C
authors.lastname: Qin
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003804:Dentin / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D015854:Up-Regulation; D055114:X-Ray Microtomography
chemical_list: D002135:Calcium-Binding Proteins; C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; C509696:FAM20C protein, mouse; C000717428:Fgf23 protein, mouse; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: Bone; DMP1; FAM20C; FGF23; dentin; hypophosphatemia