title: PTHrP Nuclear Localization and Carboxyl Terminus Sequences Modulate Dental and Mandibular Development in Part via the Action of p27.
abstract: To determine whether the action of the PTHrP nuclear localization sequence 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 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 with wild-type mice; however, these parameters were partly rescued in p27(-/-) Pthrp(KI/KI) mice compared with 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 nuclear localization sequence to regulate dental and mandibular development.
authors: State Key Laboratory of Reproductive Medicine (W.S., J.W., L.H., H.L., R.W., D.M.), The Research Center for Bone and Stem Cells, Department of Anatomy, Histology, and Embryology, Nanjing Medical University, Nanjing 210029, Jiangsu, People's Republic of China; and Lady Davis Institute for Medical Research (A.K.), Jewish General Hospital, and Calcium Research Laboratory (D.G.), McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada H3A 1A1.
authors: Wen
authors: W
authors: Sun
authors: State Key Laboratory of Reproductive Medicine (W.S., J.W., L.H., H.L., R.W., D.M.), The Research Center for Bone and Stem Cells, Department of Anatomy, Histology, and Embryology, Nanjing Medical University, Nanjing 210029, Jiangsu, People's Republic of China; and Lady Davis Institute for Medical Research (A.K.), Jewish General Hospital, and Calcium Research Laboratory (D.G.), McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada H3A 1A1.
authors: Jun
authors: J
authors: Wu
authors: State Key Laboratory of Reproductive Medicine (W.S., J.W., L.H., H.L., R.W., D.M.), The Research Center for Bone and Stem Cells, Department of Anatomy, Histology, and Embryology, Nanjing Medical University, Nanjing 210029, Jiangsu, People's Republic of China; and Lady Davis Institute for Medical Research (A.K.), Jewish General Hospital, and Calcium Research Laboratory (D.G.), McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada H3A 1A1.
authors: Linying
authors: L
authors: Huang
authors: State Key Laboratory of Reproductive Medicine (W.S., J.W., L.H., H.L., R.W., D.M.), The Research Center for Bone and Stem Cells, Department of Anatomy, Histology, and Embryology, Nanjing Medical University, Nanjing 210029, Jiangsu, People's Republic of China; and Lady Davis Institute for Medical Research (A.K.), Jewish General Hospital, and Calcium Research Laboratory (D.G.), McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada H3A 1A1.
authors: Hong
authors: H
authors: Liu
authors: State Key Laboratory of Reproductive Medicine (W.S., J.W., L.H., H.L., R.W., D.M.), The Research Center for Bone and Stem Cells, Department of Anatomy, Histology, and Embryology, Nanjing Medical University, Nanjing 210029, Jiangsu, People's Republic of China; and Lady Davis Institute for Medical Research (A.K.), Jewish General Hospital, and Calcium Research Laboratory (D.G.), McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada H3A 1A1.
authors: Rong
authors: R
authors: Wang
authors: State Key Laboratory of Reproductive Medicine (W.S., J.W., L.H., H.L., R.W., D.M.), The Research Center for Bone and Stem Cells, Department of Anatomy, Histology, and Embryology, Nanjing Medical University, Nanjing 210029, Jiangsu, People's Republic of China; and Lady Davis Institute for Medical Research (A.K.), Jewish General Hospital, and Calcium Research Laboratory (D.G.), McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada H3A 1A1.
authors: Andrew
authors: A
authors: Karaplis
authors: State Key Laboratory of Reproductive Medicine (W.S., J.W., L.H., H.L., R.W., D.M.), The Research Center for Bone and Stem Cells, Department of Anatomy, Histology, and Embryology, Nanjing Medical University, Nanjing 210029, Jiangsu, People's Republic of China; and Lady Davis Institute for Medical Research (A.K.), Jewish General Hospital, and Calcium Research Laboratory (D.G.), McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada H3A 1A1.
authors: David
authors: D
authors: Goltzman
authors: State Key Laboratory of Reproductive Medicine (W.S., J.W., L.H., H.L., R.W., D.M.), The Research Center for Bone and Stem Cells, Department of Anatomy, Histology, and Embryology, Nanjing Medical University, Nanjing 210029, Jiangsu, People's Republic of China; and Lady Davis Institute for Medical Research (A.K.), Jewish General Hospital, and Calcium Research Laboratory (D.G.), McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada H3A 1A1.
authors: Dengshun
authors: D
authors: Miao
mesh_terms: D000539:Alveolar Process / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D003804:Dentin / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008334:Mandible / Q000254:growth & development / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D044162:Parathyroid Hormone-Related Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27