Compressive Force Strengthened the Pro-inflammatory Effect of Zoledronic Acid on Il-1ß Stimulated Human Periodontal Fibroblasts

Overview

Journal Clin Oral Investig

Specialty Dentistry

Date 2020 Nov 10

PMID 33169272

Citations 2

Authors

Sarah Grimm

Ambili Mundethu

Judit Symmank

Christoph Hennig

Christian Walter

Elisabeth Reichardt

Heiner Wehrbein

Collin Jacobs

Affiliations

Soon will be listed here.

Abstract

Objectives: The number of patients in dentistry taking bisphosphonates (BP) increases every year. There are only little data about the influence of biomechanical stress due to orthodontic treatment and periodontal inflammation in BP patients. This study focused on the effects of the induced inflammation by IL-1ß in compressed human periodontal ligament fibroblasts (HPdLF) exposed to the nitrogen-containing BP zoledronate in vitro.

Materials And Methods: HPdLF were incubated with 5 μmol/l zoledronate and 10 ng/ml IL-1ß for 48 h. In the last 3 h, cells were exposed to a compressive, centrifugal force of 34.9 g/cm. Cell viability was analyzed directly after the compressive force by MTT assay. Gene expression of COX-2 and IL-6 was investigated using quantitative qRT-PCR. PGE-2 and IL-6 protein secretion were measured via ELISA.

Results: The cell viability of HPdLF was not affected. Without inflammatory pre-stimulation, COX-2 expression was increased by compression and zoledronate. IL-6 expression was increased under compression. On secretion level, the combination of compression and zoledronate induced a slightly increase of IL-6 secretion. In contrast, inflammatory pre-stimulation strengthened the compressive upregulation of COX-2, as well as induced a higher PGE-2 secretion. Further addition of zoledronate to pre-stimulated cells additionally strengthened the compression-induced upregulation of COX-2 and IL-6 expression as well as protein secretion compared to all other groups.

Conclusions: Biomechanical stress might trigger a pro-inflammatory potential of BP further enhanced in the presence of an inflammatory pre-stimulation.

Clinical Relevance: To prevent excessive host inflammatory responses, occlusal overloading and mechanical stress due to orthodontic treatment should be avoided in BP patients with untreated periodontitis.

Citing Articles

Effect of the antirheumatic medication methotrexate (MTX) on biomechanical compressed human periodontal ligament fibroblasts (hPDLFs).

Welte-Jzyk C, Plumer V, Schumann S, Pautz A, Erbe C BMC Oral Health. 2024; 24(1):329.

PMID: 38475789 PMC: 10936030. DOI: 10.1186/s12903-024-04092-1.

GDF15 Modulates the Zoledronic-Acid-Induced Hyperinflammatory Mechanoresponse of Periodontal Ligament Fibroblasts.

Nitzsche A, Hennig C, von Brandenstein K, Doding A, Schulze-Spate U, Symmank J Cells. 2024; 13(2).

PMID: 38247838 PMC: 10814077. DOI: 10.3390/cells13020147.

References

Van Poznak C . The use of bisphosphonates in patients with breast cancer. Cancer Control. 2003; 9(6):480-9. DOI: 10.1177/107327480200900605. View

Wysowski D, Greene P . Trends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002-2012. Bone. 2013; 57(2):423-8. DOI: 10.1016/j.bone.2013.09.008. View

Herrera I, Kam Y, Whittaker T, Champion M, Ajlan R . Bisphosphonate-induced orbital inflammation in a patient on chronic immunosuppressive therapy. BMC Ophthalmol. 2019; 19(1):51. PMC: 6374910. DOI: 10.1186/s12886-019-1063-8. View

Pozzi S, Vallet S, Mukherjee S, Cirstea D, Vaghela N, Santo L . High-dose zoledronic acid impacts bone remodeling with effects on osteoblastic lineage and bone mechanical properties. Clin Cancer Res. 2009; 15(18):5829-39. DOI: 10.1158/1078-0432.CCR-09-0426. View

Diel I, Bergner R, Grotz K . Adverse effects of bisphosphonates: current issues. J Support Oncol. 2008; 5(10):475-82. View

Nancollas G, Tang R, Phipps R, Henneman Z, Gulde S, Wu W . Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2005; 38(5):617-27. DOI: 10.1016/j.bone.2005.05.003. View

Walter C, Klein M, Pabst A, Al-Nawas B, Duschner H, Ziebart T . Influence of bisphosphonates on endothelial cells, fibroblasts, and osteogenic cells. Clin Oral Investig. 2009; 14(1):35-41. DOI: 10.1007/s00784-009-0266-4. View

Jung J, Park J, Righesso L, Pabst A, Al-Nawas B, Kwon Y . Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro. Clin Oral Investig. 2018; 22(7):2527-2534. DOI: 10.1007/s00784-018-2349-6. View

Pabst A, Ziebart T, Koch F, Taylor K, Al-Nawas B, Walter C . The influence of bisphosphonates on viability, migration, and apoptosis of human oral keratinocytes--in vitro study. Clin Oral Investig. 2011; 16(1):87-93. DOI: 10.1007/s00784-010-0507-6. View

10.

Meikle M . The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 years after Carl Sandstedt. Eur J Orthod. 2006; 28(3):221-40. DOI: 10.1093/ejo/cjl001. View

11.

Kirschneck C, Fanghanel J, Wahlmann U, Wolf M, Roldan J, Proff P . Interactive effects of periodontitis and orthodontic tooth movement on dental root resorption, tooth movement velocity and alveolar bone loss in a rat model. Ann Anat. 2016; 210:32-43. DOI: 10.1016/j.aanat.2016.10.004. View

12.

Kirschneck C, Maurer M, Wolf M, Reicheneder C, Proff P . Regular nicotine intake increased tooth movement velocity, osteoclastogenesis and orthodontically induced dental root resorptions in a rat model. Int J Oral Sci. 2017; 9(3):174-184. PMC: 5709548. DOI: 10.1038/ijos.2017.34. View

13.

Kirschneck C, Meier M, Bauer K, Proff P, Fanghanel J . Meloxicam medication reduces orthodontically induced dental root resorption and tooth movement velocity: a combined in vivo and in vitro study of dental-periodontal cells and tissue. Cell Tissue Res. 2017; 368(1):61-78. DOI: 10.1007/s00441-016-2553-0. View

14.

Suzuki Y, Nishiyama T, Hasuda K, Fujishiro T, Niikura T, Hayashi S . Effect of etidronate on COX-2 expression and PGE(2) production in macrophage-like RAW 264.7 cells stimulated by titanium particles. J Orthop Sci. 2007; 12(6):568-77. DOI: 10.1007/s00776-007-1180-8. View

15.

Liu L, Igarashi K, Kanzaki H, Chiba M, Shinoda H, Mitani H . Clodronate inhibits PGE(2) production in compressed periodontal ligament cells. J Dent Res. 2006; 85(8):757-60. DOI: 10.1177/154405910608500813. View

16.

Kanasi E, Ayilavarapu S, Jones J . The aging population: demographics and the biology of aging. Periodontol 2000. 2016; 72(1):13-8. DOI: 10.1111/prd.12126. View

17.

Proff P, Reicheneder C, Faltermeier A, Kubein-Meesenburg D, Romer P . Effects of mechanical and bacterial stressors on cytokine and growth-factor expression in periodontal ligament cells. J Orofac Orthop. 2014; 75(3):191-202. DOI: 10.1007/s00056-014-0212-1. View

18.

Walter C, Pabst A, Ziebart T, Klein M, Al-Nawas B . Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts and osteoblasts in vitro. Oral Dis. 2010; 17(2):194-9. DOI: 10.1111/j.1601-0825.2010.01720.x. View

19.

Jacobs C, Schramm S, Dirks I, Walter C, Pabst A, Meila D . Mechanical loading increases pro-inflammatory effects of nitrogen-containing bisphosphonate in human periodontal fibroblasts. Clin Oral Investig. 2017; 22(2):901-907. DOI: 10.1007/s00784-017-2168-1. View

20.

Nokhbehsaim M, Winter J, Rath B, Jager A, Jepsen S, Deschner J . Effects of enamel matrix derivative on periodontal wound healing in an inflammatory environment in vitro. J Clin Periodontol. 2011; 38(5):479-90. DOI: 10.1111/j.1600-051X.2010.01696.x. View