Zafar, S, Cullinan, MP, Drummond, BK orcid.org/0000-0002-5786-5879 et al. (2 more authors) (2020) Effects of zoledronic acid and geranylgeraniol on angiogenic gene expression in primary human osteoclasts. Journal of Oral Science, 62 (1). pp. 79-83. ISSN 1343-4934
Abstract
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with bisphosphonate treatment. Zoledronic acid (ZA) is a commonly used bisphosphonate due to its effectiveness in increasing bone density and reducing skeletal events, with evidence that it alters angiogenesis. Replacement of the mevalonate pathway using geranylgeraniol (GGOH) was studied to determine the effects of ZA on angiogenic gene expression in primary human osteoclasts. Osteoclast cultures were generated from peripheral blood mononuclear cells of three patients using the peripheral blood mononuclear cell isolation. These cells were phenotyped by phase-contrast microscopy, tartrate-resistant acid phosphatase staining, and pit assays. Primary osteoclasts were found to express a number of key angiogenic molecules at very high levels. Gene expression levels for 84 human angiogenic factors were determined using PCR arrays. Three genes with significant fold regulation (FR) in response to ZA were as follows: tumor necrosis factor (FR = +2.57, P = 0.050), CXCL9 (FR = +39.48, P = 0.028), and CXCL10 (FR = +18.52, P = 0.0009). The co-addition of geranylgeraniol with ZA resulted in the significant down-regulation of these three genes along with CCL2, TGFBR1, ENG, and CXCL1. GGOH reversed the gene changes induced by ZA and may offer a promising treatment for BRONJ.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 by Nihon University School of Dentistry. This is an author produced version of an article published in Journal of Oral Science. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | bisphosphonate-related osteonecrosis of the jaw; geranylgeraniol; mevalonate pathway; osteoclasts; zoledronic acid |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Paediatric Dentistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 06 Oct 2020 15:19 |
Last Modified: | 25 Jun 2023 22:27 |
Status: | Published |
Publisher: | Nihon University School of Dentistry |
Identification Number: | 10.2334/josnusd.19-0130 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:166351 |