Senescent human periodontal ligament fibroblasts after replicative exhaustion or ionizing radiation have a decreased capacity towards osteoblastic differentiation.
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.
Laboratory of Cell Proliferation & Ageing, Institute of Biosciences & Applications, NCSR "Demokritos", 153 10, Athens, Greece.
Dimitrios
D
Konstantonis
Adamantia
A
Papadopoulou
Margarita
M
Makou
Theodore
T
Eliades
Efthimia K
EK
Basdra
Dimitris
D
Kletsas
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000528:radiation effects*; D054338:Cell Transdifferentiation / Q000528:radiation effects*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000528:radiation effects*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D005786:Gene Expression Regulation; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism / Q000528:radiation effects*; D010513:Periodontal Ligament / Q000378:metabolism / Q000528:radiation effects*; D012333:RNA, Messenger / Q000378:metabolism
D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D012333:RNA, Messenger; C493709:RUNX2 protein, human; D000469:Alkaline Phosphatase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2