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

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Objectives The aim of this study was to investigate in vitro the effect of clodronate on interleukin-1ß (IL-1ß)–stimulated human periodontal ligament fibroblasts (HPdLFs) with the focus on inflammatory factors of… Click to show full abstract

Objectives The aim of this study was to investigate in vitro the effect of clodronate on interleukin-1ß (IL-1ß)–stimulated human periodontal ligament fibroblasts (HPdLFs) with the focus on inflammatory factors of orthodontic tooth movement with and without compressive force. Materials and methods HPdLFs were incubated with 5 μM clodronate and 10 ng/mL IL-1ß. After 48 h, cells were exposed to 3 h of compressive force using a centrifuge. The gene expression of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), matrix metalloproteinase 8 (MMP-8), and the tissue inhibitor of MMP (TIMP-1) was analyzed using RT-PCR. Prostaglandin E2 (PGE-2), IL-6, and TIMP-1 protein syntheses were quantified via ELISA. Results Compressive force and IL-1ß induced an overexpression of COX-2 gene expression (61.8-fold; p  < 0.05 compared with control), diminished by clodronate (41.1-fold; p  < 0.05 compared with control). Clodronate slowed down the compression and IL-1ß induced IL-6 gene expression (161-fold vs. 85.6-fold; p  < 0.05 compared with control). TNF-α was only slightly affected without statistical significance. Clodronate reduced IL-1ß-stimulated MMP-8 expression with and without compressive force. TIMP-1 on gene and protein level was downregulated in all groups. Analyzing the MMP-8/TIMP-1 ratio, the highest ratio was detected in IL-1ß-stimulated HPdLFs with compressive force (21.2-fold; p  < 0.05 compared with control). Clodronate diminished IL-1ß-induced upregulation of MMP-8/TIMP-1 ratio with (11.5-fold; p  < 0.05 compared with control) and without (12.5-fold; p  < 0.05 compared with control) compressive force. Conclusion Our study demonstrates a slightly anti-inflammatory effect by clodronate under compressive force in vitro. Additionally, the periodontal remodeling presented by the MMP-8/TIMP-1 ratio seems to be diminished by clodronate. Clinical relevance Reduction of pro-inflammatory factors and reduction of periodontal remodeling might explain reduced orthodontic tooth movement under clodronate intake.

Keywords: fold compared; compressive force; timp; force; clodronate; compared control

Journal Title: Clinical Oral Investigations
Year Published: 2019

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