Skip to main content

Advertisement

Log in

Effect of CBX7 deficiency on the socket healing after tooth extractions

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

CBX7 is shown to down-regulate the expression of osteopontin (OPN) that is associated with osteoblast function. Here, we studied the role of CBX7 in the wound healing of tooth extraction socket in which osteoblast activity is critical via comparison between CBX7-knockout (CBX7−/−) mice and their wild-type (WT) counterparts of 6 weeks old with maxillary first molar extracted. Mice were euthanized at 7, 14, and 21 days after extractions, and alveolar sockets were assessed by semi-quantitative histomorphometry for hard tissue healing, including new bone fill (Masson’s trichrome staining), osteoblast activity (OPN/osterix, Osx), osteoclast activity (tartrate-resistant acid phosphatase, TRAP), and for soft tissue healing, including blood vessels (alpha smooth muscle actin, α-SMA). Also, the bone microarchitecture was evaluated by micro-CT. In radiological analysis, CBX7−/− mice increased bone mass significantly more than WT mice did. Consistently, both the amount of new bone fill and OPN/Osx-immunopositive cells in the extraction sockets were significantly increased in CBX7−/− mice at each time point with respect to their WT siblings, while osteoclast number exhibited a trend of more increase in CBX7−/− mice at all time points as well. In agreement with enhanced bone formation during socket healing, significantly elevated α-SMA-immunopositive area was noted in CBX7−/− mice in contrast to WT mice. Taken together, these data suggest that CBX7 deficiency has a positive effect on tooth extraction socket healing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Forzati F, Federico A, Pallante P, Abbate A, Esposito F, Malapelle U, Sepe R, Palma G, Troncone G, Scarfo M, Arra C, Fedele M, Fusco A (2013) CBX7 is a tumor suppressor in mice and humans (vol 122, pg 612, 2012). J Clin Investig 123:934. https://doi.org/10.1172/jci68754

    Article  CAS  Google Scholar 

  2. Sepe R, Formisano U, Federico A, Forzati F, Bastos AU, D’Angelo D, Cacciola NA, Fusco A, Pallante P (2015) CBX7 and HMGA1b proteins act in opposite way on the regulation of the SPP1 gene expression. Oncotarget 6:2680–2692

    Article  PubMed  PubMed Central  Google Scholar 

  3. Denhardt DT, Noda M (1998) Osteopontin expression and function: role in bone remodeling. J Cell Biochem Suppl 30–31:92–102

    Article  PubMed  Google Scholar 

  4. 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. https://doi.org/10.1021/bi00223a029

    Article  CAS  PubMed  Google Scholar 

  5. 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 106:401–407

    Article  CAS  PubMed  Google Scholar 

  6. 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. https://doi.org/10.1093/rheumatology/ken385

    Article  CAS  PubMed  Google Scholar 

  7. Standal T, Borset M, Sundan A (2004) Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp Oncol 26:179–184

    CAS  PubMed  Google Scholar 

  8. Zhou Z, Yin Y, Jiang F, Niu Y, Wan S, Chen N, Shen M (2016) CBX7 deficiency plays a positive role in dentin and alveolar bone development. J Mol Histol 47:401–411. https://doi.org/10.1007/s10735-016-9682-3

    Article  CAS  PubMed  Google Scholar 

  9. Araujo MG, Silva CO, Misawa M, Sukekava F (2015) Alveolar socket healing: what can we learn? Periodontology 2000 68:122–134. https://doi.org/10.1111/prd.12082

    Article  PubMed  Google Scholar 

  10. Guglielmotti MB, Cabrini RL (1985) Alveolar wound healing and ridge remodeling after tooth extraction in the rat: a histologic, radiographic, and histometric study. J Oral Maxillofac Surg 43:359–364. https://doi.org/10.1016/0278-2391(85)90257-5

    Article  CAS  PubMed  Google Scholar 

  11. Trombelli L, Farina R, Marzola A, Bozzi L, Liljenberg B, Lindhe J (2008) Modeling and remodeling of human extraction sockets. J Clin Periodontol 35:630–639. https://doi.org/10.1111/j.1600-051X.2008.01246.x

    Article  PubMed  Google Scholar 

  12. Sparmann A, van Lohuizen M (2006) Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer 6:846–856. https://doi.org/10.1038/nrcd1991

    Article  CAS  PubMed  Google Scholar 

  13. Cao R, Tsukada Y, Zhang Y (2005) Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell 20:845–854. https://doi.org/10.1016/j.molcel.2005.12.002

    Article  CAS  PubMed  Google Scholar 

  14. Wang SW, Robertson GP, Zhua JY (2004) A novel human homologue of Drosophila polycomb like gene is up-regulated in multiple cancers. Gene 343:69–78. https://doi.org/10.1016/j.gene.2004.09.006

    Article  CAS  PubMed  Google Scholar 

  15. Pallante P, Forzati F, Federico A, Arra C, Fusco A (2015) Polycomb protein family member CBX7 plays a critical role in cancer progression. Am J Cancer Res 5:1594–1601

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Rittling SR, Matsumoto HN, McKee MD, Nanci A, An XR, Novick KE, Kowalski AJ, Noda M, Denhardt DT (1998) Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro. J Bone Miner Res 13:1101–1111. https://doi.org/10.1359/jbmr.1998.13.7.1101

    Article  CAS  PubMed  Google Scholar 

  17. Kuboki Y, Hashimoto F, Ishibashi K (1988) Time-dependent changes of collagen crosslinks in the socket after tooth extraction in rabbits. J Dent Res 67:944–948. https://doi.org/10.1177/00220345880670061101

    Article  CAS  PubMed  Google Scholar 

  18. Lin WL, McCulloch CA, Cho MI (1994) Differentiation of periodontal ligament fibroblasts into osteoblasts during socket healing after tooth extraction in the rat. Anat Rec 240:492–506. https://doi.org/10.1002/ar.1092400407

    Article  CAS  PubMed  Google Scholar 

  19. Lekic P, Rojas J, Birek C, Tenenbaum H, McCulloch CAG (2001) Phenotypic comparison of periodontal ligament cells in vivo and in vitro. J Periodontal Res 36:71–79. https://doi.org/10.1034/j.1600-0765.2001.360202.x

    Article  CAS  PubMed  Google Scholar 

  20. Cardaropoli G, Araujo M, Lindhe J (2003) Dynamics of bone tissue formation in tooth extraction sites—an experimental study in dogs. J Clin Periodontol 30:809–818. https://doi.org/10.1034/j.1600-051X.2003.00366.x

    Article  CAS  PubMed  Google Scholar 

  21. Cardaropoli G, Araujo M, Hayacibara R, Sukekava F, Lindhe J (2005) Healing of extraction sockets and surgically produced—augmented and non-augmented—defects in the alveolar ridge. An experimental study in the dog. J Clin Periodontol 32:435–440. https://doi.org/10.1111/j.1600-051X.2005.00692.x

    Article  CAS  PubMed  Google Scholar 

  22. Kanyama M, Kuboki T, Akiyama K, Nawachi K, Miyauchi FM, Yatani H, Kubota S, Nakanishi T, Takigawa M (2003) Connective tissue growth factor expressed in rat alveolar bone regeneration sites after tooth extraction. Arch Oral Biol 48:723–730. https://doi.org/10.1016/s0003-9969(03)00153-5

    Article  CAS  PubMed  Google Scholar 

  23. Sato H, Takeda Y (2007) Proliferative activity, apoptosis, and histogenesis in the early stages of rat tooth extraction wound healing. Cells Tissues Organs 186:104–111. https://doi.org/10.1159/000103513

    Article  CAS  PubMed  Google Scholar 

  24. Schropp L, Wenzel A, Kostopoulos L, Karring T (2003) Bone healing and soft tissue contour changes following single-tooth extraction: a clinical and radiographic 12-month prospective study. Int J Periodontics Restor Dent 23:313–323

    Google Scholar 

  25. Chen J-H, Chen Y-C, Mao C-L, Chiou J-M, Tsao CK, Tsai K-S (2014) Association between secreted phosphoprotein-1 (SPP1) polymorphisms and low bone mineral density in women. PLoS One. https://doi.org/10.1371/journal.pone.0097428

    Article  PubMed  PubMed Central  Google Scholar 

  26. Horner A, Bishop NJ, Bord S, Beeton C, Kelsall AW, Coleman N, Compston JE (1999) Immunolocalisation of vascular endothelial growth factor (VEGF) in human neonatal growth plate cartilage. J Anat 194:519–524. https://doi.org/10.1046/j.1469-7580.1999.19440519.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Saran U, Piperni SG, Chatterjee S (2014) Role of angiogenesis in bone repair (in English). Arch Biochem Biophys 561:109–117. https://doi.org/10.1016/j.abb.2014.07.006

    Article  CAS  PubMed  Google Scholar 

  28. Kennedy A, Ng CT, Biniecka M, Saber T, Taylor C, O’Sullivan J, Veale DJ, Fearon U (2010) Angiogenesis and blood vessel stability in inflammatory arthritis. Arthritis Rheum 62:711–721. https://doi.org/10.1002/art.27287

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported in part by the National Basic Research Program of China (2012CB966902), the National Natural Science Foundation of China (81670966), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, 2014-37) and the Project of Invigorating College through Science and Education.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Zhixuan Zhou or Ning Chen.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to disclose.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. S1

Tooth extraction of mouse upper left first molar. a Preparation of mouse and instruments. b Position of the elevator blade between 1st and 2nd molars. c Morphology of tooth extraction socket. The yellow dotted lines depict the locations of three roots, including mesio-, distobuccal and distopalatal root (M, DB and DP). d Shape of mouse upper left first molar without any fractures (JPEG 4219 kb)

Fig. S2

CBX7 expression in post-extraction sockets of WT mice. Representative photomicrograph of extraction wound sections stained immunochemically for CBX7. Bar, 100 μm (JPEG 628 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, F., Yang, X., Meng, X. et al. Effect of CBX7 deficiency on the socket healing after tooth extractions. J Bone Miner Metab 37, 584–593 (2019). https://doi.org/10.1007/s00774-018-0958-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-018-0958-4

Keywords

Navigation