Abstract
To clarify the role of CBX7 deficiency in dentin and alveolar bone development, the dental and mandibular phenotypes of homozygous CBX7-knockout (CBX7−/−) mice were compared with their wild-type (WT) counterparts at 3 weeks age. In contrast to WT littermates, dental volume and dentin sialoprotein-positive area were significantly increased, whereas the area ratio of predentin to dentin was decreased markedly in CBX7−/− mice. Mineral density, cortical thickness, alveolar bone volume, type I collagen and osterix-immunopositive area, osteoblast number and activity, protein expression and mRNA level of Runt-related transcription factor 2 (Runx2), alkaline phosphatase, osteocalcin, osteopontin and bone morphogenetic protein 2 (BMP2) were all remarkably increased, while osteoclast number and activity, and mRNA expression ratio of NF-κB ligand (RANKL) to osteoprotegerin (opg) were all decreased significantly in the alveolar bone of CBX7−/− mice compared with their WT counterparts. Moreover, proliferating cell nuclear antigen (PCNA)-positive cells were found more in Hertwig’ s epithelial root sheath of CBX7−/− mice, and their protein level of cyclin E1, cyclin-dependent kinase 2 (CDK2) were correspondingly increased in contrast to WT mice. Taken together, these results of this study suggest that CBX7 deficiency plays a positive role in dentin and alveolar bone formation.
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Bernard D et al (2005) CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus. Oncogene 24:5543–5551. doi:10.1038/sj.onc.1208735
Bethel M, Chitteti BR, Srour EF, Kacena MA (2013) The changing balance between osteoblastogenesis and adipogenesis in aging and its impact on hematopoiesis. Curr Osteoporosis Rep 11:99–106. doi:10.1007/s11914-013-0135-6
Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342. doi:10.1038/nature01658
Brakus SM, Govorko DK, Vukojevic K, Jakus IA, Carev D, Petricevic J, Saraga-Babic M (2010) Apoptotic and anti-apoptotic factors in early human mandible development. Eur J Oral Sci 118:537–546. doi:10.1111/j.1600-0722.2010.00777.x
Caetano-Lopes J, Canhao H, Fonseca JE (2007) Osteoblasts and bone formation. Acta Reumatol Port 32:103–110
Chellaiah MA et al (2003) Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression. Mol Biol Cell 14:173–189. doi:10.1091/mbc.E02-06-0354
Chen M et al (2014) Low-dose X-ray irradiation promotes osteoblast proliferation, differentiation and fracture healing. PLoS ONE 9:e104016. doi:10.1371/journal.pone.0104016
Choi JY et al (1996) Expression patterns of bone-related proteins during osteoblastic differentiation in MC3T3-E1 cells. J Cell Biochem 61:609–618. doi:10.1002/(sici)1097-4644(19960616)61:4<609:aid-jcb15>3.0.co;2-a
Choi ST, Kim JH, Kang EJ, Lee SW, Park MC, Park YB, Lee SK (2008) Osteopontin might be involved in bone remodelling rather than in inflammation in ankylosing spondylitis. Rheumatology 47:1775–1779. doi:10.1093/rheumatology/ken385
Denhardt DT, Noda M (1998) Osteopontin expression and function: role in bone remodeling. J Cell Biochem 72(S30–31):92–102
Forzati F, et al. (2013) CBX7 is a tumor suppressor in mice and humans (vol 122, pg 612, 2012). J Clin Investig 123:934. doi:10.1172/jci68754
Forzati F et al (2014) CBX7 gene expression plays a negative role in adipocyte cell growth and differentiation. Biol Open 3:871–879. doi:10.1242/bio.20147872
Gil J, Bernard D, Martinez D, Beach D (2004) Polycomb CBX7 has a unifying role in cellular lifespan. Nat Cell Biol 6:67–72. doi:10.1038/ncb1077
Gray-Bablin J, Zalvide J, Fox MP, Knickerbocker CJ, DeCaprio JA, Keyomarsi K (1996) Cyclin E, a redundant cyclin in breast cancer. Proc Natl Acad Sci USA 93:15215–15220. doi:10.1073/pnas.93.26.15215
Johnson DG, Walker CL (1999) Cyclins and cell cycle checkpoints. Annu Rev Pharmacol Toxicol 39:295–312. doi:10.1146/annurev.pharmtox.39.1.295
Lee SK, Kim YS, Oh HS, Yang KH, Kim EC, Chi JG (2001) Prenatal development of the human mandible. Anat Rec 263:314–325. doi:10.1002/ar.1110
Li Z, Yu M, Tian W (2013) An inductive signalling network regulates mammalian tooth morphogenesis with implications for tooth regeneration. Cell Prolif 46:501–508. doi:10.1111/cpr.12051
Linde A, Goldberg M (1993) Dentinogenesis. Crit Rev Oral Biol Med 4:679–728
Lorentowicz-Zagalak M, Przystanska A, Wozniak W (2005) The development of Meckel’s cartilage in staged human embryos during the 5th week. Folia morphol 64:23–28
McBride-Gagyi SH, McKenzie JA, Buettmann EG, Gardner MJ, Silva MJ (2015) Bmp2 conditional knockout in osteoblasts and endothelial cells does not impair bone formation after injury or mechanical loading in adult mice. Bone 81:533–543. doi:10.1016/j.bone.2015.09.003
McKee MD, Glimcher MJ, Nanci A (1992) High-resolution immunolocalization of osteopontin and osteocalcin in bone and cartilage during endochondral ossification in the chicken tibia. Anat Rec 234:479–492. doi:10.1002/ar.1092340404
Miao DS, Scutt A (2002) Recruitment, augmentation and apoptosis of rat osteoclasts in 1,25-(OH)(2)D-3 response to short-term treatment with 1,25-dihydroxyvitamin D-3 in vivo. BMC Musculoskelet Disord. doi:10.1186/1471-2474-3-16
Miao DS, Bai XY, Panda D, McKee MD, Karaplis AC, Goltzman D (2001) Osteomalacia in Hyp mice is associated with abnormal Phex expression and with altered bone matrix protein expression and deposition. Endocrinology 142:926–939. doi:10.1210/en.142.2.926
Miao DS, He B, Karaplis AC, Goltzman D (2002) Parathyroid hormone is essential for normal fetal bone formation. J Clin Investig 109:1173–1182. doi:10.1172/jci200214817
Moore MA, Gotoh Y, Rafidi K, Gerstenfeld LC (1991) Characterization of a cDNA for chicken osteopontin: expression during bone development, osteoblast differentiation, and tissue distribution. Biochemistry 30:2501–2508. doi:10.1021/bi00223a029
Nakashima K, Zhou X, Kunkel G, Zhang ZP, Deng JM, Behringer RR, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor Osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29. doi:10.1016/s0092-8674(01)00622-5
Pallante P et al (2008) Loss of the CBX7 gene expression correlates with a highly malignant phenotype in thyroid cancer. Cancer Res 68:6770–6778. doi:10.1158/0008-5472.can-08-0695
Panda DK, Miao DS, Bolivar I, Li JR, Huo RJ, Hendy GN, Goltzman D (2004) Inactivation of the 25-hydroxyvitamin D 1 alpha-hydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis. J Biol Chem 279:16754–16766. doi:10.1074/jbc.M310271200
Pockwinse SM et al (2006) Microtubule-dependent nuclear-cytoplasmic shuttling of RUNX2. J Cell Physiol 206:354–362. doi:10.1002/jcp.20469
Ritchie HH, Pinero GJ, Hou H, Butler WT (1995) Molecular analysis of rat dentin sialoprotein. Connect Tissue Res 33:73–79. doi:10.3109/03008209509016985
Schuettengruber B, Chourrout D, Vervoort M, Leblanc B, Cavalli G (2007) Genome regulation by polycomb and trithorax proteins. Cell 128:735–745. doi:10.1016/j.cell.2007.02.009
Sears RC, Nevins JR (2002) Signaling networks that link cell proliferation and cell fate. J Biol Chem 277:11617–11620. doi:10.1074/jbc.R100063200
Sepe R et al (2015) CBX7 and HMGA1b proteins act in opposite way on the regulation of the SPP1 gene expression. Oncotarget 6:2680–2692
Sun W et al (2010) Alterations in phosphorus, calcium and PTHrP contribute to defects in dental and dental alveolar bone formation in calcium-sensing receptor-deficient mice. Development 137:985–992. doi:10.1242/dev.045898
Wu JI, Lessard J, Crabtree GR (2009) Understanding the words of chromatin regulation. Cell 136:200–206. doi:10.1016/j.cell.2009.01.009
Xu T et al (1998) Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nat Genet 20:78–82
Xue YB, Karaplis AC, Hendy GN, Goltzman D, Miao DS (2005) Genetic models show that parathyroid hormone and 1,25-dihydroxyvitamin D-3 play distinct and synergistic roles in postnatal mineral ion homeostasis and skeletal development. Hum Mol Genet 14:1515–1528. doi:10.1093/hmg/ddi160
Yin Y, Wang Q, Sun W, Wang Y, Chen N, Miao D (2014) p27(kip1) deficiency accelerates dentin and alveolar bone formation. Clin Exp Pharmacol Physiol 41:807–816. doi:10.1111/1440-1681.12276
Zeichner-David M, Oishi K, Su Z, Zakartchenko V, Chen LS, Arzate H, Bringas P Jr (2003) Role of Hertwig’s epithelial root sheath cells in tooth root development. Dev Dyn 228:651–663. doi:10.1002/dvdy.10404
Zohar R, Cheifetz S, McCulloch CA, Sodek J (1998) Analysis of intracellular osteopontin as a marker of osteoblastic cell differentiation and mesenchymal cell migration. Eur J Oral Sci 106(Suppl 1):401–407
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This study was supported in part by the National Basic Research Program of China (2012CB966902), the National Natural Science Foundation of China (81271109), and The Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, 2014-37). The authors have no conflicts of interest to disclose.
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Zhixuan Zhou and Ying Yin have contributed equally to this work.
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Zhou, Z., Yin, Y., Jiang, F. et al. CBX7 deficiency plays a positive role in dentin and alveolar bone development. J Mol Hist 47, 401–411 (2016). https://doi.org/10.1007/s10735-016-9682-3
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DOI: https://doi.org/10.1007/s10735-016-9682-3