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The cytotoxic effects of three different bisphosphonates in-vitro on human gingival fibroblasts,osteoblasts and osteogenic sarcoma cells
Authors:Y. Açil  B. Möller  P. Niehoff  K. Rachko  V. Gassling  J. Wiltfang  M.J.K. Simon
Affiliation:1. Department of Oral and Maxillofacial Surgery (Head: Prof. Dr. Dr. Jörg Wiltfang), UK S-H, Campus Kiel, Arnold-Heller-Strasse 3, Haus 26, 24105 Kiel, Germany;2. Department of Radiotherapy (Radiooncology) (Head: Prof. Dr. Dr. Bernhard Kimmig), UK S-H, Campus Kiel, Arnold-Heller-Strasse 3, Haus 23, 24105 Kiel, Germany;1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia;2. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York;2. Division of Nuclear Medicine, Department of Radiology, Upstate Medical University, State University of New York, Syracuse, NY;3. Division of Nuclear Medicine, Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;1. Department of Radiation Oncology, La Princesa University Hospital, Madrid, Spain;2. Spanish National Cancer Research Centre (CNIO), Madrid, Spain;3. Department of Pathology, University Hospital Henares, Madrid, Spain;4. Department of Pathology, La Princesa University Hospital, Madrid, Spain;5. Department of Urology, La Princesa University Hospital, Madrid, Spain;6. Department of Urology, University Hospital Henares, Madrid, Spain;1. The Cancer Centre, Queen Elizabeth Hospital, Birmingham, University Hospitals Birmingham NHS Trust, UK;2. School of Cancer Sciences, University of Birmingham, Birmingham, UK;3. Cancer Research Unit, Clinical Trials Unit, University of Warwick, Coventry, UK;1. Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA;2. Servicio de Oncologia Medica, Hospital Universitario La Paz, Madrid, Spain
Abstract:IntroductionOsteonecrosis of the jaw (ONJ) is an emerging condition in patients undergoing long-term administration of bisphosphonates (BP) for the treatment of osteoporosis and hypercalcaemia associated with malignancy, multiple myeloma, and metastatic breast and prostate cancers. This is a follow-up study, its purpose was to examine the effects in-vitro of intravenous zoledronic acid (ZOL) and pamidronate (PAM) and oral alendronate (FOS) on the human oral cavity using gingival fibroblasts and osteoblasts cells and, in addition, osteogenic sarcoma cells (SaOS-2-cells).Materials and methodsHuman gingival fibroblasts, osteoblasts and SaOS-2-cells were seeded on multiple 6-well plates at a density of 5 × 105 cells in a 4-week cell culture. Four different concentrations (1, 5, 10, 20 μM) of each BP (ZOL, PAM, FOS) and pyrophosphate were used in this study.ResultsAll BP decreased collagen production and lowered cell proliferation in-vitro. ZOL was the component with most inhibitory effect.ConclusionThe findings in this study suggest that ZOL, PAM and FOS generally diminish cell proliferation and collagen production of human gingival fibroblasts, osteoblasts and SaOS-2-cells. The present follow-up study shows that not only ZOL and PAM but also FOS have a strong inhibitory effect on collagen production and cell survival in-vitro.
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