{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:07:06Z","timestamp":1777417626291,"version":"3.51.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cyclic tensile stretching (CTS) induces osteoblastic differentiation of periodontal ligament fibroblasts (PDLF). On the other hand, increased concentrations of tumour necrosis factor-\u03b1 (TNF-\u03b1) are found in inflammatory conditions, leading to periodontal disease and tooth loss. Accordingly, our aim was to investigate the short- and long-term effect of TNF-\u03b1 on the response of human PDLF to CTS and its implication on osteoblastic differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PDLF were either pre-incubated for 4 hours or were repeatedly exposed to TNF-\u03b1 for up to 50 days and then subjected to CTS. Gene expression was determined by quantitative real-time polymerase chain reaction. Activation of mitogen-activated protein kinase (MAPK) was monitored by western analysis and cell proliferation by bromodeoxyuridine incorporation. Intracellular reactive oxygen species were determined by the 2\u00b4, 7\u00b4-dichlorofluorescein-diacetate assay and osteoblastic differentiation by Alizarin Red-S staining after an osteo-inductive period of 21 days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CTS of PDLF induced an immediate upregulation of the c-fos transcription factor and, further downstream the overexpression of alkaline phosphatase and osteopontin, two major osteoblast marker genes. A 4-hour pre-incubation with TNF-\u03b1 repressed these effects. Similarly, long-term propagation of PDLF along with TNF-\u03b1 diminished their osteoblastic differentiation capacity and suppressed cells\u2019 CTS-elicited responses. The observed phenomena were not linked with TNF-\u03b1-induced premature senescence or oxidative stress. While CTS induced the activation of MAPKs, involved in mechanotransduction, TNF-\u03b1 treatment provoked a small delay in the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Increased concentrations of TNF-\u03b1, such as those recorded in many inflammatory diseases, suppress PDLF\u2019s immediate responses to mechanical forces compromising their osteoblastic differentiation potential, possibly leading to tissue\u2019s impaired homeostasis.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ejo\/cjaa042","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T03:21:43Z","timestamp":1592968903000},"page":"396-406","source":"Crossref","is-referenced-by-count":7,"title":["Short- and long-term treatment with TNF-\u03b1 inhibits the induction of osteoblastic differentiation in cyclic tensile-stretched periodontal ligament fibroblasts"],"prefix":"10.1093","volume":"42","author":[{"given":"Adamantia","family":"Papadopoulou","sequence":"first","affiliation":[{"name":"Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research \u2018Demokritos\u2019, Ag. 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