TABLE 4.

The effects of GGOH on other cells.

Authors (years)	Study design	Major findings
Cozin et al. (2011)	Primary gingival fibroblasts were exposed to zoledronate or pamidronate with or without GGOH.	GGOH alone is inert to the cells
		GGOH ↑ cell proliferation and migration, ↓ adhesion defect (cell-substratum adhesion and F-actin bundles) caused by zoledronate effectively (3 × 10−5 M) and not pamidronate (6 × 10−5 M)
Ziebart et al. (2011)	Commercially available HUVEC and human gingival fibroblasts cultured with BPs with or without GGOH for 72 h. All BPs at 5 × 10−5 M, GGOH at 10−5 M	HUVEC: GGOH ↑ cell viability and migration suppressed by ibandronate and zoledronate
		Fibroblasts: GGOH ↑ cell viability suppressed by zoledronate; ↑ cell migration by ibandronate, pamidronate and zoledronate
		GGOH cellular cytoskeletal distortion in cells exposed to all BPs
Zafar et al. (2014)	Human gingival fibroblasts from 5 female patients were cultured with 3 × 10−5 M zoledronate with or without farnesol (10−5 M) or GGOH (5 × 10−5 M) for 72 h	GGOH alone ↓ cell viability but ↑ cell viability in the presence of zoledronate
		GGOH preserves the morphology of cells exposed to zoledronate
		GGOH ↓ BMP2 and VEGF-A expression induced by zoledronate
Hagelauer et al. (2015)	Commercialised human gingival fibroblasts and HUVEC were treated with zoledronate, GGOH, farnesol or other isoprenoids	GGOH alone: High dose (5 × 10−5–10−4 M) ↓ cell viability, no effects on migration (10−5–10−6 M)
		GGOH + zoledronate: ↑ cell viability and migration suppressed by zoledronate at all concentrations (10−5–10−6 M)
		GGOH reverses destructive cellular morphology

Abbreviation↓, decrease; ↑, increase; BMP-2, bone morphogenetic protein-2; BP, bisphosphonate; HUVEC, human umbilical vein endothelial cells; GGOH, geranylgeraniol; VEGF-A, vascular endothelial growth factor-A.