Biogerontology

, Volume 14, Issue 6, pp 741–751 | Cite as

Senescent human periodontal ligament fibroblasts after replicative exhaustion or ionizing radiation have a decreased capacity towards osteoblastic differentiation

  • Dimitrios Konstantonis
  • Adamantia Papadopoulou
  • Margarita Makou
  • Theodore Eliades
  • Efthimia K. Basdra
  • Dimitris Kletsas
Research Article

Abstract

Loss of teeth increases with age or after genotoxic treatments, like head and neck radiotherapy, due to periodontium breakdown. Periodontal ligament fibroblasts represent the main cell type in this tissue and are crucial for the maintenance of homeodynamics and for its regeneration. Here, we have studied the characteristics of human periodontal ligament fibroblasts (hPDLF) that became senescent after replicative exhaustion or after exposure to ionizing radiation, as well as their ability for osteoblastic differentiation. We found that senescent hPDLF express classical markers of senescence, as well as a catabolic phenotype, as shown by the decrease in collagen type I and the increase of MMP-2 expression. In addition, we observed a considerably decreased expression of the major transcription factor for osteoblastic differentiation, i.e. Runx2, a down-regulation which was found to be p53-dependent. In accordance to the above, senescent cells have a significantly decreased alkaline phosphatase gene expression and activity, as well as a reduced ability for osteoblastic differentiation, as found by Alizarin Red staining. Interestingly, cells from both type of senescence express similar characteristics, implying analogous functions in vivo. In conclusion, senescent hPDLF express a catabolic phenotype and express a significantly decreased ability towards an osteoblastic differentiation, thus probably affecting tissue development and integrity.

Keywords

Periodontal ligament fibroblasts Senescence Osteoblastic differentiation Runx2 ALP 

Supplementary material

10522_2013_9449_MOESM1_ESM.ppt (142 kb)
Effect of a single 4-Gy dose of ionizing radiation on early passage hPDL fibroblasts. Cells were irradiated with 4 Gy of ionizing radiation in 60Co source, and cell lysates, collected at the indicated time-points, were subjected to Western blot analysis by using specific antibodies. Actin levels were used as internal loading control. Supplementary material (PPT 143 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Dimitrios Konstantonis
    • 1
    • 2
  • Adamantia Papadopoulou
    • 1
  • Margarita Makou
    • 2
  • Theodore Eliades
    • 3
  • Efthimia K. Basdra
    • 4
  • Dimitris Kletsas
    • 1
  1. 1.Laboratory of Cell Proliferation & Ageing, Institute of Biosciences & ApplicationsNCSR “Demokritos”AthensGreece
  2. 2.Department of Orthodontics, School of DentistryUniversity of AthensAthensGreece
  3. 3.Department of Orthodontics and Paediatric DentistryUniversity of ZurichZurichSwitzerland
  4. 4.Cellular and Molecular Biomechanics Unit, Department of Biological ChemistryUniversity of Athens Medical SchoolAthensGreece

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