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Interactions between BMP-7 and USAG-1 (uterine sensitization-associated gene-1) regulate supernumerary organ formations.

Kiso H, Takahashi K, Saito K, Togo Y, Tsukamoto H, Huang B, Sugai M, Shimizu A, Tabata Y, Economides AN, Slavkin HC, Bessho K - PLoS ONE (2014)

Bottom Line: BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced.Based upon these results, we conclude that USAG-1 functions as an antagonist of BMP-7 in this model system.These results further suggest that the phenotypes of USAG-1 and BMP-7 mutant mice reported provide opportunities for regenerative medicine and dentistry.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, Japan.

ABSTRACT
Bone morphogenetic proteins (BMPs) are highly conserved signaling molecules that are part of the transforming growth factor (TGF)-beta superfamily, and function in the patterning and morphogenesis of many organs including development of the dentition. The functions of the BMPs are controlled by certain classes of molecules that are recognized as BMP antagonists that inhibit BMP binding to their cognate receptors. In this study we tested the hypothesis that USAG-1 (uterine sensitization-associated gene-1) suppresses deciduous incisors by inhibition of BMP-7 function. We learned that USAG-1 and BMP-7 were expressed within odontogenic epithelium as well as mesenchyme during the late bud and early cap stages of tooth development. USAG-1 is a BMP antagonist, and also modulates Wnt signaling. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Using explant culture and subsequent subrenal capsule transplantation of E15 USAG-1 mutant maxillary incisor tooth primordia supplemented with BMP-7 demonstrated in USAG-1+/- as well as USAG-1-/- rescue and supernumerary tooth development. Based upon these results, we conclude that USAG-1 functions as an antagonist of BMP-7 in this model system. These results further suggest that the phenotypes of USAG-1 and BMP-7 mutant mice reported provide opportunities for regenerative medicine and dentistry.

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BMP-7 has potential to partially induce the formation of maxillary supernumerary incisors formation in vitro.Enhanced BMP-7 rescue the formation of maxillary incisor supernumerary tooth in E15 USAG-1 mutant mice in organ culture and subrenal capsule assay. The incisor explants supplemented with BMP-7 in USAG-1+/− (E and H) and USAG-1−/− (F and I) have supernumerary tooth in similar incidence after 20 days of culture, whereas these cultured explants in USAG-1+/+ (D and G) maintained the normal tooth number. (A–C) Explant appearance. (D–F) Coronal and (G–I) sagittal sections of explant. (J–L) Sagittal sections of control explant. (M) Table showing the relationship between number of teeth of explants and USAG-1 phenotypes.
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pone-0096938-g006: BMP-7 has potential to partially induce the formation of maxillary supernumerary incisors formation in vitro.Enhanced BMP-7 rescue the formation of maxillary incisor supernumerary tooth in E15 USAG-1 mutant mice in organ culture and subrenal capsule assay. The incisor explants supplemented with BMP-7 in USAG-1+/− (E and H) and USAG-1−/− (F and I) have supernumerary tooth in similar incidence after 20 days of culture, whereas these cultured explants in USAG-1+/+ (D and G) maintained the normal tooth number. (A–C) Explant appearance. (D–F) Coronal and (G–I) sagittal sections of explant. (J–L) Sagittal sections of control explant. (M) Table showing the relationship between number of teeth of explants and USAG-1 phenotypes.

Mentions: To test whether BMP-7 actually induces supernumerary tooth formation, we performed explant culture and subsequent subrenal kidney capsule transplantation of E15 USAG-1 mutant maxillary incisor tooth primordia supplemented with BMP-7. We previously showed that the USAG-1+/− mice showed phenotypically normal tooth number and position in maxillary incisor as well as wild type [15]. The incisor explants supplemented with BMP-7 in USAG-1+/− as well as USAG-1−/− have supernumerary tooth in similar numbers after 20 days culture, while these cultured explants in USAG-1+/+ presented normal tooth number (Fig.6A–J). These results demonstrated BMP-7 has a partial potential to induce supernumerary tooth formation, however it was not readily observed to induce extra tooth organs only with BMP-7.


Interactions between BMP-7 and USAG-1 (uterine sensitization-associated gene-1) regulate supernumerary organ formations.

Kiso H, Takahashi K, Saito K, Togo Y, Tsukamoto H, Huang B, Sugai M, Shimizu A, Tabata Y, Economides AN, Slavkin HC, Bessho K - PLoS ONE (2014)

BMP-7 has potential to partially induce the formation of maxillary supernumerary incisors formation in vitro.Enhanced BMP-7 rescue the formation of maxillary incisor supernumerary tooth in E15 USAG-1 mutant mice in organ culture and subrenal capsule assay. The incisor explants supplemented with BMP-7 in USAG-1+/− (E and H) and USAG-1−/− (F and I) have supernumerary tooth in similar incidence after 20 days of culture, whereas these cultured explants in USAG-1+/+ (D and G) maintained the normal tooth number. (A–C) Explant appearance. (D–F) Coronal and (G–I) sagittal sections of explant. (J–L) Sagittal sections of control explant. (M) Table showing the relationship between number of teeth of explants and USAG-1 phenotypes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016158&req=5

pone-0096938-g006: BMP-7 has potential to partially induce the formation of maxillary supernumerary incisors formation in vitro.Enhanced BMP-7 rescue the formation of maxillary incisor supernumerary tooth in E15 USAG-1 mutant mice in organ culture and subrenal capsule assay. The incisor explants supplemented with BMP-7 in USAG-1+/− (E and H) and USAG-1−/− (F and I) have supernumerary tooth in similar incidence after 20 days of culture, whereas these cultured explants in USAG-1+/+ (D and G) maintained the normal tooth number. (A–C) Explant appearance. (D–F) Coronal and (G–I) sagittal sections of explant. (J–L) Sagittal sections of control explant. (M) Table showing the relationship between number of teeth of explants and USAG-1 phenotypes.
Mentions: To test whether BMP-7 actually induces supernumerary tooth formation, we performed explant culture and subsequent subrenal kidney capsule transplantation of E15 USAG-1 mutant maxillary incisor tooth primordia supplemented with BMP-7. We previously showed that the USAG-1+/− mice showed phenotypically normal tooth number and position in maxillary incisor as well as wild type [15]. The incisor explants supplemented with BMP-7 in USAG-1+/− as well as USAG-1−/− have supernumerary tooth in similar numbers after 20 days culture, while these cultured explants in USAG-1+/+ presented normal tooth number (Fig.6A–J). These results demonstrated BMP-7 has a partial potential to induce supernumerary tooth formation, however it was not readily observed to induce extra tooth organs only with BMP-7.

Bottom Line: BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced.Based upon these results, we conclude that USAG-1 functions as an antagonist of BMP-7 in this model system.These results further suggest that the phenotypes of USAG-1 and BMP-7 mutant mice reported provide opportunities for regenerative medicine and dentistry.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, Japan.

ABSTRACT
Bone morphogenetic proteins (BMPs) are highly conserved signaling molecules that are part of the transforming growth factor (TGF)-beta superfamily, and function in the patterning and morphogenesis of many organs including development of the dentition. The functions of the BMPs are controlled by certain classes of molecules that are recognized as BMP antagonists that inhibit BMP binding to their cognate receptors. In this study we tested the hypothesis that USAG-1 (uterine sensitization-associated gene-1) suppresses deciduous incisors by inhibition of BMP-7 function. We learned that USAG-1 and BMP-7 were expressed within odontogenic epithelium as well as mesenchyme during the late bud and early cap stages of tooth development. USAG-1 is a BMP antagonist, and also modulates Wnt signaling. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Using explant culture and subsequent subrenal capsule transplantation of E15 USAG-1 mutant maxillary incisor tooth primordia supplemented with BMP-7 demonstrated in USAG-1+/- as well as USAG-1-/- rescue and supernumerary tooth development. Based upon these results, we conclude that USAG-1 functions as an antagonist of BMP-7 in this model system. These results further suggest that the phenotypes of USAG-1 and BMP-7 mutant mice reported provide opportunities for regenerative medicine and dentistry.

Show MeSH
Related in: MedlinePlus