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This study determined the effect of the bisphosphonate, zoledronic acid and the replenishment of the<jats:styled-content style=\"fixed-case\">MVP<\/jats:styled-content>by geranylgeraniol on human gingival fibroblasts. Cell viability, apoptosis, morphological analysis using transmission electron microscopy, and gene expression for vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B, epiregulin and interferon\u2010alpha were conducted. Results showed cellular viability was decreased in the presence of zoledronic acid and the co\u2010addition of zoledronic acid with geranylgeraniol restored cell viability to control levels. Caspase 3\/7 was detected in zoledronic\u2010acid\u2010treated cells indicating apoptosis. Transmission electron microscopy revealed dilation of the rough endoplasmic reticulum with zoledronic acid and the appearance of multiple lipid\u2010like vesicles following the addition of geranylgeraniol. Zoledronic acid significantly (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05,<jats:styled-content style=\"fixed-case\">FR<\/jats:styled-content>\u00a0&gt;\u00a0\u00b12) up\u2010regulated vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B and epiregulin at one or more time points but not interferon\u2010alpha. Addition of geranylgeraniol resulted in a reduction in the expression of all five genes compared with zoledronic\u2010acid\u2010treated human gingival fibroblasts. The study concluded geranylgeraniol partially reversed the effects of zoledronic acid in human gingival fibroblasts both at the cellular and genetic levels, suggesting the regulation of these genes is mediated via the mevalonate pathway.<\/jats:p>","DOI":"10.1111\/jop.12181","type":"journal-article","created":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T04:53:11Z","timestamp":1398401591000},"page":"711-721","source":"Crossref","is-referenced-by-count":34,"title":["Zoledronic acid and geranylgeraniol regulate cellular behaviour and angiogenic gene expression in human gingival fibroblasts"],"prefix":"10.1111","volume":"43","author":[{"given":"S.","family":"Zafar","sequence":"first","affiliation":[{"name":"Faculty of Dentistry Sir John Walsh Research Institute University of Otago Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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