Reduction of alkaline phosphatase activity in aged human osteogenic periodontal ligament fibroblasts exhibiting short telomeres

Abstract

The osteogenic cell type of human periodontal ligament fibroblasts (PDLF) undergoes senescence at finite population doubling numbers unrelated to donor ages. This study investigated telomere lengths of osteogenic PDLF from differently aged donors and alterations of the osteoblast-like properties in the aged PDLF with short telomeres. Telomere lengths of osteogenic PDLF were biased towards long or short among all 15- to 51-year-old individuals, and did not show a normal distribution by Pearson's test or a correlation to donor age by simple regression analysis. In osteogenic PDLF, senescence-associated beta-galactosidase was expressed in 78.5% of cells in the clones with short telomeres (mean 3.02 kbp), and in 9.4% of cells in the clones with long telomeres (mean 13.06 kbp). These results suggest that human periodontium comprises aged osteogenic PDLF without correlation to age. Osteogenic PDLF with long telomeres strongly expressed alkaline phosphatase (ALPase) activity whereas cells with short telomeres expressed ALPase activity to a weaker extent. Total activity of ALPase in the clones of osteogenic PDLF with long telomeres was significantly higher than that in the clones with short telomeres. The produced amounts of both osteopontin and osteocalcin in the clones of osteogenic PDLF with long telomeres were slightly but statistically significantly smaller than those in the clones with short telomeres. These findings suggest that aged osteogenic PDLF reduce the expression of ALPase activity but that there is not a critical alteration in bone-associated protein production. Aged osteogenic PDLF may impair the ability to induce ALPase-dependent calcification.

Aging affects the phenotypic characteristics of human periodontal ligament cells and the cellular response to hormonal stimulation in vitro

“…1B). In support of this and mirroring the data of the present study, in vitro experiments in human periodontal ligament cells showed an age-dependent reduction of alkaline phosphatase specific activity (14). One might speculate that the apparent discrepancy between the decrease in ALP activity (Fig.…”

Implications of cultured periodontal ligament cells for the clinical and experimental setting: A review

“…(72). In addition, the telomere length of osteogenic PDL cells did not show correlation with donor age, but did correlate with a reduction in alkaline phosphatase activity (83). Therefore, donor age seems to affect the in vitro life span of PDL fibroblasts.…”

Age-related changes of fibroblast density in the human periodontal ligament

“…This however does not lead to an accumulation of senescent cell populations in the periodontal ligament of aged donors as Sawa et al [17] showed. Moxham and Evans [18] even found ultrastructural changes in periodontal ligament cells from aged animals indicating a decrease in collagen producing activity.…”