Ullrich, Niklas and Schroeder, Agnes and Jantsch, Jonathan and Spanier, Gerrit and Proff, Peter and Kirschneck, Christian (2019) The role of mechanotransduction versus hypoxia during simulated orthodontic compressive strain-an in vitro study of human periodontal ligament fibroblasts. INTERNATIONAL JOURNAL OF ORAL SCIENCE, 11: UNSP 33. ISSN 1674-2818, 2049-3169
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During orthodontic tooth movement (OTM) mechanical forces trigger pseudo-inflammatory, osteoclastogenic and remodelling processes in the periodontal ligament (PDL) that are mediated by PDL fibroblasts via the expression of various signalling molecules. Thus far, it is unknown whether these processes are mainly induced by mechanical cellular deformation (mechanotransduction) or by concomitant hypoxic conditions via the compression of periodontal blood vessels. Human primary PDL fibroblasts were randomly seeded in conventional six-well cell culture plates with O-2-impermeable polystyrene membranes and in special plates with gas-permeable membranes (Lumox (R), Sarstedt), enabling the experimental separation of mechanotransducive and hypoxic effects that occur concomitantly during OTM. To simulate physiological orthodontic compressive forces, PDL fibroblasts were stimulated mechanically at 2 g.cm(-2) for 48 h after 24 h of pre-incubation. We quantified the cell viability by MTT assay, gene expression by quantitative real-time polymerase chain reaction (RT-qPCR) and protein expression by western blot/enzyme-linked immunosorbent assays (ELISA). In addition, PDL-fibroblast-mediated osteoclastogenesis (TRAP(+) cells) was measured in a 72-h coculture with RAW264.7 cells. The expression of HIF-1 alpha, COX-2, PGE2, VEGF, COL1A2, collagen and ALPL, and the RANKL/OPG ratios at the mRNA/protein levels during PDL-fibroblast-mediated osteoclastogenesis were significantly elevated by mechanical loading irrespective of the oxygen supply, whereas hypoxic conditions had no significant additional effects. The cellular-molecular mediation of OTM by PDL fibroblasts via the expression of various signalling molecules is expected to be predominantly controlled by the application of force (mechanotransduction), whereas hypoxic effects seem to play only a minor role. In the context of OTM, the hypoxic marker HIF-1 alpha does not appear to be primarily stabilized by a reduced O-2 supply but is rather stabilised mechanically.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECEPTOR ACTIVATION; HIF-1 ACTIVATION; TOOTH MOVEMENT; TENSION FORCE; UP-REGULATION; OSTEOCLASTOGENESIS; EXPRESSION; CELLS; LIPOPOLYSACCHARIDE; BONE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2020 08:20 |
| Last Modified: | 25 Mar 2020 08:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25864 |
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