Transgenic expression of Dspp partially rescued the long bone defects of Dmp1-null mice

Abstract

Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) belong to the Small Integrin-Binding Ligand N-linked Glycoprotein (SIBLING) family. In addition to the features common to all SIBLING members, DMP1 and DSPP share several unique similarities in chemical structure, proteolytic activation and tissue localization. Mutations in, or deletion of DMP1, cause autosomal recessive hypophosphatemic rickets along with dental defects; DSPP mutations or its ablation are associated with dentinogenesis imperfecta. While the roles and functional mechanisms of DMP1 in osteogenesis have been extensively studied, those of DSPP in long bones have been studied only to a limited extent. Previous studies by our group revealed that transgenic expression of Dspp completely rescued the dentin defects of Dmp1-null (Dmp1−/−) mice. In this investigation, we assessed the effects of transgenic Dspp on osteogenesis by analyzing the formation and mineralization of the long bones in Dmp1−/− mice that expresses a transgene encoding full-length DSPP driven by a 3.6-kb rat Col1a1 promoter (referred as “Dmp1−/−;Dspp-Tg mice”). We characterized the long bones of the Dmp1−/−;Dspp-Tg mice at different ages and compared them with those from Dmp1−/− and Dmp1+/− (normal control) mice. Our analyses showed that the long bones of Dmp1−/−;Dspp-Tg mice had a significant increase in cortical bone thickness, bone volume and mineral density along with a remarkable restoration of trabecular thickness compared to those of the Dmp1−/− mice. The long bones of Dmp1−/−;Dspp-Tg mice underwent a dramatic reduction in the amount of osteoid, significant improvement of the collagen fibrillar network, and better organization of the lacunocanalicular system, compared to the Dmp1−/− mice. The elevated levels of biglycan, bone sialoprotein and osteopontin in Dmp1−/− mice were also noticeably corrected by the transgenic expression of Dspp. These findings suggest that DSPP and DMP1 may function synergistically within the complex milieus of bone matrices.

Yunnan Baiyao Conditioned Medium Promotes the Odonto/Osteogenic Capacity of Stem Cells from Apical Papilla via Nuclear Factor Kappa B Signaling Pathway

“…In detail, DSP, DSPP, and DMP1 are responsible for dentin formation and the precisely oriented hydroxyapatite crystals initiation in calcifying matrices [32]. DSPP may act as a downstream effector molecule of DMP1 during dentinogenesis.…”

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

“…Dentin matrix protein-1 (DMP1) is expressed in odontoblasts that secrete the matrix proteins in the process of dentinogenesis and mineralization during postnatal tooth development. Some studies have suggested a potential functional and synergistical relationship between DSPP and DMP1 , in which DSPP acts as the downstream effector molecule of DMP1 and can be controlled by DMP1 during the dentinogenesis and osteogenesis272829.…”

Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells

“…Cell lyses containing equal amount of β-actin were loaded onto 5–15% SDS-PAGE to follow the protocol as previously described [13]. The the primary antibody against FGF23 was monoclonal mouse IgG [14]. The antibodies against the phosphorylated and total phosphorylated Smad1/5/8, p-38 and Erk were all polyclonal rabbit IgG purchased from Santa Cruz Biotechnology.…”