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Mechanical force application and inflammation induce osteoclastogenesis by independent pathways

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Abstract

Objective

To investigate the functional changes of PDL fibroblasts in the presence of mechanical force, inflammation, or a combination of force and inflammation.

Materials and methods

Inflammatory supernatants were prepared by inoculating human neutrophils with Porphyromonas gingivalis. Primary human PDL fibroblasts (PDLF), gingival fibroblasts (GFs), and osteoblasts (Saos2) were then exposed to the inflammatory supernatants. Orthodontic force on the PDLFs was simulated by centrifugation. Analyses included cell proliferation, cell viability, cell cycle, and collagen expression, as well as osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL) expression.

Results

Mechanical force did not affect PDLF viability, but it increased the metabolic rate compared to resting cells. Force application shifted the PDLF cell cycle to the G0/G1 phase, arresting cell proliferation and leading to elevated collagen production, mild OPG level elevation, and robust RANKL level elevation. Including an inflammatory supernatant in the presence of force did not affect PDLF viability, proliferation, or cytokine expression. By contrast, the inflammatory supernatant increased RANKL expression in GFs, but not in Saos2 cells.

Conclusion

Applying mechanical force significantly affects PDLF function. Although inflammation had no effect on PDLF or Saos2 cells, it promoted RANKL expression in GF cells. Within the limitations of the in vitro model, the results suggest that periodontal inflammation and mechanical forces could affect bone catabolism through effects on different cell types, which may culminate in synergistic bone resorption.

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Data Availability

The data that support the findings of this study are available on request from the corresponding author.

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Contributions

T.C. conceived the ideas, collected the data, analyzed the data, and contributed to the writing, revisions, and final approval of the manuscript. Y.I. collected the data, analyzed the data, and contributed to the writing. R.T.N. analyzed the data and contributed to the writing. A.S. analyzed the data and contributed to the writing, revisions, and final approval of the manuscript. L.S. analyzed the data and contributed to the writing, revisions, and final approval of the manuscript. D.P. conceived the ideas, collected the data, analyzed the data, and contributed to the writing, revisions, and final approval of the manuscript. All authors reviewed the manuscript.

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Correspondence to David Polak.

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Experiments involving human tissues were conducted according to the approval of the Helsinki committee of the Hadassah—Hebrew University Medical Center (approval number HMO-12–144-08).

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Lior Shapira and David Polak have equal contribution to the study.

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Chachartchi, T., Itai, Y., Tzach-Nahman, R. et al. Mechanical force application and inflammation induce osteoclastogenesis by independent pathways. Clin Oral Invest 27, 5853–5863 (2023). https://doi.org/10.1007/s00784-023-05196-8

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