Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

21 February 2009

Cyclosporine A, but not tacrolimus, is associated with impaired proliferation and differentiation of human osteoblast-like cells in vitro

Rodrigo Oliveira MoreiraABCDEF, Leandro Souza ThiagoABDE, Felipe Leite OliveiraABDE, Alex BalduinoABDEF, Radovan BorojevicDEG, Maria Eugenia Leite DuarteADEFG, Maria Lucia Fleiuss FariasADEFG

Med Sci Monit 2009; 15(3): BR65-70 :: ID: 869575

Abstract

Background
The prevention of graft rejection after liver transplant with cyclosporine A (CyA) and tacrolimus has been associated to decreased bone mineral density. The aim of this study was to investigate the in vitro effects of increasing concentrations of CyA and tacrolimus on human osteoblasts.
Material and Method
Human osteoblast-like cells obtained by the outgrowth of cells from bone chips were exposed to tacrolimus (10-1000 ng/mL) or CyA (1000-50,000 ng/mL). Alkaline phosphatase (ALP) activity was determined on days 2, 4, 6, and 8, and cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell counting on days 2, 4, 6, and 8. Cell death was investigated by flow cytometry with propidium iodine, and apoptosis was assessed by flow cytometry with fluorescently conjugated annexin V.
Results
No effects of tacrolimus were detected with respect to ALP activity or cell proliferation. In CyA-treated cultures, concentrations greater than 10 000 ng/mL were associated with decreased ALP activity after 8 days (P<0.05). In addition, a dose-dependent reduction in cell proliferation was detected after 6 days (P<0.05). This decreased cell proliferation was associated with increased apoptosis in response to 50 000 ng/mL CyA.
Conclusions
Our results showed that CyA reduced, in a time- and concentration-dependent manner, the number of metabolically active cells via a decrease in proliferation and an increase in cell death, and induced impairment of osteoblast differentiation. These negative effects of CyA on human osteoblast-like cells might contribute to the bone loss reported in vivo.

Keywords: Staining and Labeling, Osteoblasts - enzymology, Cyclosporine - pharmacology, Dose-Response Relationship, Drug, Cells, Cultured, Cell Survival - drug effects, Cell Proliferation - drug effects, Cell Differentiation - drug effects, Cell Count, Annexins - metabolism, Alkaline Phosphatase - metabolism, Tacrolimus - pharmacology

Add Comment 0 Comments

924 6

Editorial

01 November 2023 : Editorial  

Editorial: Factors Driving New Variants of SARS-CoV-2, Immune Escape, and Resistance to Antiviral Treatments as the End of the COVID-19 Pandemic is Declared

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville,

DOI: 10.12659/MSM.942960

Med Sci Monit 2023; 29:e942960

0:00

In Press

28 Nov 2023 : Clinical Research  

Impact of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography on Therapeutic Decisions and ...

Med Sci Monit In Press; DOI: 10.12659/MSM.942122  

28 Nov 2023 : Clinical Research  

Long-Term Outcomes of Decompression and Grafting in Acute Pathological Proximal Femur Fractures in Children...

Med Sci Monit In Press; DOI: 10.12659/MSM.943031  

27 Nov 2023 : Clinical Research  

Comparison of Outcomes from Emergency Admissions to a Major Trauma Center in Turkey of 1646 Elderly Patient...

Med Sci Monit In Press; DOI: 10.12659/MSM.942916  

27 Nov 2023 : Clinical Research  

Evaluating Modified Ultrasound-Guided Serratus Anterior Plane Block for Enhanced Postoperative Recovery in ...

Med Sci Monit In Press; DOI: 10.12659/MSM.942757  

Most Viewed Current Articles

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

0:00

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750