title: Roles of DMP1 processing in osteogenesis, dentinogenesis and chondrogenesis.
abstract: Dentin matrix protein 1 (DMP1) is an acidic protein that plays critical roles in osteogenesis and dentinogenesis. Protein chemistry studies have demonstrated that DMP1 primarily exists as processed NH₂⁻ and COOH-terminal fragments in the extracellular matrix of bone and dentin. Our earlier work showed that the substitution of Asp²¹³ (a residue at a cleavage site) by Ala²¹³ blocks the processing of mouse DMP1 in vitro. Recently, we generated transgenic mice expressing this mutant DMP1 (designated 'D213A-DMP1'). By crossbreeding these transgenic mice with Dmp1-knockout (Dmp1-KO) mice, we obtained mice expressing the D213A-DMP1 transgene in the Dmp1-null background (named 'Dmp1-KO/D213A-Tg' mice). In this study, we analyzed the long bone, mandible, dentin, and cartilage of Dmp1-KO/D213A-Tg mice in comparison with wild-type, Dmp1-KO, and Dmp1-KO mice expressing the normal DMP1 transgene (Dmp1-KO/normal-Tg). Our results showed that D213A-DMP1 was barely cleaved in the dentin matrix of Dmp1-KO/D213A-Tg mice and the expression of D213A-DMP1 failed to rescue the developmental defects in Dmp1-null mice. Interestingly, enlarged growth plates and condylar cartilages were observed in Dmp1-KO/D213A-Tg mice, indicating a potential role of the full-length form of DMP1 in chondrogenesis.
authors.affiliation: Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M Health Science Center, Dallas, Tex., USA. cqin@bcd.tamhsc.edu
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Su
authors.initials: S
authors.lastname: Ma
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
authors.forename: Chunlin
authors.initials: C
authors.lastname: Qin
mesh_terms: D000818:Animals; D055395:Bone Morphogenetic Protein 1 / Q000378:metabolism; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis; D003804:Dentin / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism; D003810:Dentinogenesis; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005269:Femur / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism; D006132:Growth Plate / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D011859:Radiography; D013977:Tibia / Q000254:growth & development / Q000378:metabolism; D014020:Tissue Extracts
chemical_list: C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; D014020:Tissue Extracts; D055395:Bone Morphogenetic Protein 1