Mechanical Loading Increases Pro-inflammatory Effects of Nitrogen-containing Bisphosphonate in Human Periodontal Fibroblasts

Overview

Journal Clin Oral Investig

Specialty Dentistry

Date 2017 Jul 9

PMID 28688092

Citations 5

Authors

Collin Jacobs

Sabrina Schramm

Isabelle Dirks

Christian Walter

Andreas Pabst

Dan Meila

Cornelius Jacobs

Heinrich Wehrbein

Affiliations

Soon will be listed here.

Abstract

Objectives: There is increasing evidence that inflammation and biomechanical loading can influence the effects of bisphosphonates (BP). The aim of this study was to investigate the influence of tensile strain application combined with IL-1ß and clodronate or zoledronate on human periodontal ligament fibroblasts (HPdLF) in vitro.

Materials And Methods: HPdLF were cultured with 10 nM IL-1ß and 5 μM clodronate or zoledronate for 48 h. Cells were applied to cyclic tensile strain (CTS; 3% elongation) for 12 h in vitro. Cell number was analyzed directly after CTS by MTT assay. Gene expression of receptor activator of cyclooxygenase-2 (COX-2) was investigated using real-time PCR. MMP-8, TIMP-1, and PGE2 were measured by ELISA. Statistics were performed with SPSS (ANOVA, p < 0.05).

Results: Zoledronate reduced the cell number of HPdLF (60.3 vs. 100%), which was significant when combined with IL-1ß. Combined with 3% CTS, this effect was voided and cell number increased over the level of the control cells. IL-1ß led to a 10-fold increase of COX-2 gene expression. Combined with CTS and zoledronate, this increase was enhanced to a gene expression 70-fold that of control cells with related PGE2 synthesis. Clodronate neither reduce the cell number nor enhanced the COX-2 gene expression. CTS increased MMP-8 protein synthesis. Combined with BP, this increase was voided. TIMP-1 protein synthesis was increased at all conditions under CTS.

Conclusions: Mechanical loading might activate cell metabolism and abolish BP- and inflammation-induced reduction of viability. Combination of mechanical loading, inflammation, and nitrogen-containing bisphosphonates can cause pro-inflammatory effects.

Clinical Relevance: Periodontal inflammation should be treated initially before BP intake to prevent decreased cell viability of the periodontium and increased inflammation, which might be enhanced by the addition of mastication forces.

Citing Articles

Effect of Tension on Human Periodontal Ligament Cells: Systematic Review and Network Analysis.

Sun C, Janjic Rankovic M, Folwaczny M, Otto S, Wichelhaus A, Baumert U Front Bioeng Biotechnol. 2021; 9:695053.

PMID: 34513810 PMC: 8429507. DOI: 10.3389/fbioe.2021.695053.

MMPs and TIMPs Expression Levels in the Periodontal Ligament during Orthodontic Tooth Movement: A Systematic Review of In Vitro and In Vivo Studies.

Behm C, Nemec M, Weissinger F, Rausch M, Andrukhov O, Jonke E Int J Mol Sci. 2021; 22(13).

PMID: 34203475 PMC: 8268288. DOI: 10.3390/ijms22136967.

Interleukin-1β Induced Matrix Metalloproteinase Expression in Human Periodontal Ligament-Derived Mesenchymal Stromal Cells under In Vitro Simulated Static Orthodontic Forces.

Behm C, Nemec M, Blufstein A, Schubert M, Rausch-Fan X, Andrukhov O Int J Mol Sci. 2021; 22(3).

PMID: 33498591 PMC: 7864333. DOI: 10.3390/ijms22031027.

Compressive force strengthened the pro-inflammatory effect of zoledronic acid on il-1ß stimulated human periodontal fibroblasts.

Grimm S, Mundethu A, Symmank J, Hennig C, Walter C, Reichardt E Clin Oral Investig. 2020; 25(6):3453-3461.

PMID: 33169272 DOI: 10.1007/s00784-020-03667-w.

Influence of clodronate and compressive force on IL-1ß-stimulated human periodontal ligament fibroblasts.

Grimm S, Wolff E, Walter C, Pabst A, Mundethu A, Jacobs C Clin Oral Investig. 2019; 24(1):343-350.

PMID: 31102041 DOI: 10.1007/s00784-019-02930-z.

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