Zoledronic acid suppresses mineralization through direct cytotoxicity and osteoblast differentiation inhibition

Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
Somying PatntirapongYodhathai Satravaha

Abstract

Zoledronic acid (ZA) is prescribed to treat various metabolic bone diseases. Despite its efficacy in preventing bone loss, ZA has been linked to osteonecrosis of the jaw in several reports. However, a mechanism underlying this occurrence is still unclear. This study was to investigate causative roles of ZA on osseous cellular activities of pre-osteoblastic cell line MC3T3-E1 (MC3T3) and mesenchymal stem cell (MSC). Morphological analysis, RT-PCR, annexin V/PI staining, together with mineralization, cell viability, and alkaline phosphatase (ALP) activity assays were performed. Zoledronic acid treatment decreased bone nodule formation at all concentrations tested (0.01-100 μM). Cell morphologies of both cell types were altered from their normal appearances after the addition of ZA (≥ 5 μM), and cell viability was significantly inhibited at concentrations ≥ 0.1 μM for MC3T3 and at concentrations ≥ 10 μM for MSC. ZA (100 μM) induced apoptosis in MC3T3 and MSC. Furthermore, ALP activity from both cells was strongly reduced when exposed to ZA (≥ 1 μM for MC3T3 and ≥ 5 μM for MSC). ZA also down-regulated Runx 2 and Col I mRNA expressions. With this in vitro study, ZA mediated defective bone mineralization by directly disrupting osteob...Continue Reading

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Citations

Jul 8, 2015·Dental Traumatology : Official Publication of International Association for Dental Traumatology·Jung Eun YooSung Chul Choi
Oct 10, 2013·Journal of Cellular Physiology·Veronica R FortinoHerman S Cheung
Sep 17, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Sharon M MoeMatthew R Allen
Nov 6, 2014·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Jiansheng SuHang Zhao
Sep 3, 2013·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Lin XiangPing Gong
Jun 6, 2018·Oral Diseases·Somying Patntirapong, Mahatana Poolgesorn
Aug 10, 2018·The Journal of International Medical Research·Henrik HoltmannRita Depprich
Jun 25, 2017·BMC Musculoskeletal Disorders·Katri KoivistoJaakko Niinimäki
Aug 28, 2020·Clinical, Cosmetic and Investigational Dentistry·Patricia Maria Wiziack ZagoMary Ann Foglio
Oct 27, 2017·Cancer Research·Stephanie RossnaglInaam A Nakchbandi
Nov 10, 2020·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Somying PatntirapongYauwaluk Suthamporn
Mar 17, 2020·Journal of the Mechanical Behavior of Biomedical Materials·Chika KoyamaKenji Mitsudo
Jun 9, 2021·European Journal of Dentistry·Charukrit LilakhunakonSomying Patntirapong

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