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PMID:26859332

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Citation

Sun, W, Wu, J, Huang, L, Liu, H, Wang, R, Karaplis, A, Goltzman, D and Miao, D' (2016) PTHrP nuclear localization and carboxyl terminus sequences modulate dental and mandibular development in part via the action of p27. Endocrinology ':en20151555

Abstract

To determine whether the action of the parathyroid hormone-related protein (PTHrP) nuclear localization sequence (NLS) and C-terminus is mediated through p27 in modulating dental and mandibular development, compound mutant mice which are homozygous for both p27 deletion and the PTHrP1-84 knock-in mutation (p27(-/-)Pthrp(KI/KI)) were generated. Their teeth and mandibular phenotypes were compared with those of p27(-/-), Pthrp(KI/KI) and wild-type (WT) mice. At 2 weeks of age, the mandibular mineral density, alveolar bone volume, osteoblast numbers and dental volume, dentin sialoprotein immunopositive areas in the first molar were increased significantly in p27(-/-) mice, and decreased dramatically in both Pthrp(KI/KI) and p27(-/-) Pthrp(KI/KI) mice compared to WT mice, however these parameters were partly rescued in p27(-/-) Pthrp(KI/KI) mice compared to Pthrp(KI/KI) mice. These data demonstrate that the deletion of p27 in Pthrp(KI/KI) mice can partially rescue defects in dental and mandibular development. Furthermore, we found that deletion of p27 in Pthrp(KI/KI) mice partially corrected the dental and mandibular phenotype by modulating cell cyclin regulating molecules and antioxidant enzymes. This study therefore indicates that the p27 pathway may function downstream in the action of PTHrP NLS to regulate dental and mandibular development.

Links

PubMed Online version:10.1210/en.2015-1555

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PTHR

GO:0005634: nucleus

ECO:0000314:

C

Fig 1 A

"The nuclear localization of C terminus PTHrP was detected using antibody against PTHrP(112–131) only in EMSCs from WT and p27-/- mice(Figure 1A)"

complete
CACAO 11367

Notes

See also

References

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