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Clin Oral Investig. 2017 Apr;21(3):771-778. doi: 10.1007/s00784-016-1842-z. Epub 2016 May 12.

The influence of geranylgeraniol on microvessel sprouting after bisphosphonate substitution in an in vitro 3D-angiogenesis assay.

Author information

1
Department of Oral and Maxillofacial Surgery, Federal Armed Forces Hospital, Rübenacherstr, 170, 56072, Koblenz, Germany. andipabst@me.com.
2
Department of Oral and Maxillofacial Surgery, University Medical Center, Augustusplatz 2, 55131, Mainz, Germany. andipabst@me.com.
3
Department of Oral and Maxillofacial Surgery, University Medical Center, Augustusplatz 2, 55131, Mainz, Germany.
4
Department of Oral and Maxillofacial Surgery, University Clinic, Georg-Voigt-Straße 3, 35039, Marburg, Germany.
5
Department of Orthodontics, University Medical Center, Augustusplatz 2, 55131, Mainz, Germany.

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.

KEYWORDS:

Angiogenesis; BP-ONJ; Bisphosphonate; Geranylgeraniol; Isoprenoid; Osteonecrosis

PMID:
27170294
DOI:
10.1007/s00784-016-1842-z
[Indexed for MEDLINE]

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