Isoprenoid Geranylgeraniol: the Influence on Cell Characteristics of Endothelial Progenitor Cells After Bisphosphonate Therapy in Vitro

Overview

Journal Clin Oral Investig

Specialty Dentistry

Date 2015 Jan 16

PMID 25589370

Citations 9

Authors

A M Pabst

M Kruger

T Ziebart

C Jacobs

C Walter

Affiliations

Soon will be listed here.

Abstract

Objectives: Geranylgeraniol (GGOH) has been reported as a potential treatment option for bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ). The aim of this study was to analyze the effects of GGOH on endothelial progenitor cells (EPC) after bisphosphonate treatment in vitro.

Materials And Methods: EPC were incubated with different nitrogen (N-BPs: ibandronate, pamidronate, zoledronate) and a non-nitrogen-containing bisphosphonates (NN-BP: clodronate) with and without GGOH. Cell viability was measured by MTT and PrestoBlue assay. Migration ability was analyzed with a Boyden and Scratch assay. Apoptosis rates were determined by colony-forming, Tunel and ToxiLight assays.

Results: Negative effects of N-BPs on EPC were shown in all tests without GGOH. The substitution of GGOH demonstrated significantly increased cell viability (MTT: p each N-BP ≤0.004; PrestoBlue: p each N-BP <0.001) and migration ability (Boyden: p each N-BP <0.001; Scratch: p each N-BP <0.001). Concerning the apoptosis rates, increased EPC colony densities (p each N-BP ≤0.009), decreased numbers of apoptotic cells in the Tunel assay (p each N-BP <0.001), and a decreased adenylate kinase release in the ToxiLight assay (p each N-BP ≤0.03) were observed. For the clodronate-treated cells, no significant differences could be detected with or without GGOH in any assay (p each N-BP/NN-BP >0.05).

Conclusions: GGOH cell treatment reversed the negative effects of bisphosphonates on EPC.

Clinical Relevance: These findings support the hypothesis that systemic or local GGOH treatment might lead to new therapeutic strategies for BP-ONJ.

Citing Articles

Significance of bisphosphonates on angiogenesis in vivo and their effect under geranyl-geraniol addition - could it alter the treatment of bisphosphonate-associated necrosis of the jaw?.

Otto M, Weigel J, Ziebart T, Lemound J Oral Maxillofac Surg. 2022; 27(2):263-268.

PMID: 35397019 DOI: 10.1007/s10006-022-01053-2.

Mechanism, prevention, and treatment for medication-related osteonecrosis of the jaws.

Pan J, Liu J Hua Xi Kou Qiang Yi Xue Za Zhi. 2021; 39(3):245-254.

PMID: 34041871 PMC: 8218254. DOI: 10.7518/hxkq.2021.03.001.

Angiogenesis in the Development of Medication-Related Osteonecrosis of the Jaws: An Overview.

Pabst A, Kruger M, Blatt S, Ziebart T, Rahimi-Nedjat R, Goetze E Dent J (Basel). 2018; 5(1).

PMID: 29563407 PMC: 5806993. DOI: 10.3390/dj5010002.

Bisphosphonates hinder osteoblastic/osteoclastic differentiation in the maxillary sinus mucosa-derived stem cells.

Zhang J, Park J, Lee J, Kwon Y, Kim E Clin Oral Investig. 2017; 22(5):1933-1943.

PMID: 29188452 DOI: 10.1007/s00784-017-2291-z.

A retrospective study of osteomyelitis and osteonecrosis of the jaws and its etiologic implication of bisphosphonate in Asians.

Hong S, Lee C, Jung J, Kim D, Walter C, Kwon Y Clin Oral Investig. 2016; 21(5):1905-1911.

PMID: 27771829 DOI: 10.1007/s00784-016-1973-2.

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