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The role of cellular senescence on the cyclic stretching-mediated activation of MAPK and ALP expression and activity in human periodontal ligament fibroblasts.

Abstract：

:Mechanical loading is considered to be a major parameter of the periodontal ligament (PDL) remodeling and differentiation. However, the molecular mechanisms that translate these forces to cellular responses are not fully elucidated. Especially, although aging affects PDL homeostasis, the role of cellular senescence on the activation of signaling pathways in periodontal ligament fibroblasts (PDLF) in response to mechanical stimulation has not been studied yet. Here, we present evidence showing that cyclic mechanical stimulation activates ERK, JNK and p38 MAPK in young (early-passage) human PDLF, in a RhoK-dependent manner. This response was found to be independent of the substratum (i.e. fibronectin or collagen) on which these cells grow. Stretching up-regulates also c-fos, a classical cellular response to mechanical deformation. Inhibition of ERK and JNK reduces, while that of p38 enhances stress-mediated c-fos expression. In addition, cyclic stretching stimulates the expression and activity of alkaline phosphatase (ALP), an early marker of osteoblastic differentiation. We have recently shown that senescent human PDLF have a significantly decreased expression of ALP, linked to an inability towards osteoblastic differentiation. Here, we found that senescent PDLF are able to respond to cyclic mechanical stretching by activating ERK, JNK and p38 MAPK, with similar kinetics compared to young cells, and by up-regulating c-fos and ALP expression and activity. However, even after stimulation, ALP levels in senescent cells are still much lower compared to the basal levels of their young counterparts, suggesting that senescence impairs the differentiation of human PDLF when subjected to cyclic mechanical deformation.

journal_name

Exp Gerontol

journal_title

Experimental gerontology

authors

Konstantonis D,Papadopoulou A,Makou M,Eliades T,Basdra E,Kletsas D

doi

10.1016/j.exger.2014.05.010

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

175-80

eissn

0531-5565

issn

1873-6815

pii

S0531-5565(14)00171-5

journal_volume

pub_type

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The role of cellular senescence on the cyclic stretching-mediated activation of MAPK and ALP expression and activity in human periodontal ligament fibroblasts.