Abstract
Objectives
Recent studies focused on angiogenesis in the pathophysiology of bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) and identified geranylgeraniol (GGOH) as a feasible option for BP-ONJ therapy. This study investigated the influence of GGOH on microvessel sprouting after BP-incubation in vitro.
Materials and methods
Ten experimental set-ups were randomly designed in an in vitro 3D-angiogenesis assay. Two groups included HUVEC cell spheroids with and without (±) GGOH substitution as controls and eight groups pairwise contained either clodronate or the nitrogen-containing bisphosphonates (N-BP) ibandronate, pamidronate, and zoledronate ± GGOH. The size of the cell spheroids including the outbranching sprouts (SpS) as well as the density (SpD) and length of the sprouts (SpL) were analyzed by a grid system after 0, 24, 48, and 72 h.
Results
For controls and NN-BP clodronate, no significant differences at any tested parameter and any point of measurement could be detected within the experimental set-ups ± GGOH (p each ≥0.05). For N-BP ibandronate, the experimental set-ups +GGOH showed a significantly increased SpS, SpD, and SpL after 48 and 72 h (p each ≤0.002) compared to the experimental set-ups −GGOH. For N-BPs pamidronate and zoledronate, the experimental set-ups + GGOH demonstrated a significantly increased SpS, SpD, and SpL after 24, 48, and 72 h (p each ≤0.001) compared to the experimental set-ups −GGOH.
Conclusions
The strong negative influence of N-BPs on microvessel sprouting could be significantly reversed by GGOH.
Clinical relevance
Since supportive therapeutic options for BP-ONJ are lacking, GGOH might be a promising substitute for BP-ONJ prevention and therapy.
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The authors give special thanks to Kathy Taylor for proof-reading and language checking.
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No fundings were received for this study. The work was supported by the Department of Oral and Maxillofacial Surgery, University Medical Center, Augustusplatz 2, 55131 Mainz, Germany.
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Pabst, A.M., Krüger, M., Sagheb, K. et al. The influence of geranylgeraniol on microvessel sprouting after bisphosphonate substitution in an in vitro 3D-angiogenesis assay. Clin Oral Invest 21, 771–778 (2017). https://doi.org/10.1007/s00784-016-1842-z
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DOI: https://doi.org/10.1007/s00784-016-1842-z