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, 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

Editorial

01 June 2024 : Editorial  

Editorial: Concerns as Highly Pathogenic Avian Influenza (HPAI) Virus of the H5N1 Subtype is Identified in Dairy Cows and Other Mammals

Dinah V. Parums

DOI: 10.12659/MSM.945315

Med Sci Monit 2024; 30:e945315

0:00

In Press

Review article  

Applications of Functional Near-Infrared Spectroscopy (fNIRS) Neuroimaging During Rehabilitation Following ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943785  

0:00

Clinical Research  

Epidemiology and Risk Factors for Revision Total Knee Arthroplasty in Chinese Patients: A Retrospective Stu...

Med Sci Monit In Press; DOI: 10.12659/MSM.943681  

Clinical Research  

Effects of the Cold Pressor Test on Popliteal Vein Diameter, Flow Velocity, and Blood Flow in the Lower Lim...

Med Sci Monit In Press; DOI: 10.12659/MSM.944560  

Clinical Research  

Outcomes of Anterior Lateral Approach and Gerdy's Tubercle Osteotomy for Tibial Plateau Fractures Involving...

Med Sci Monit In Press; DOI: 10.12659/MSM.943946  

Most Viewed Current Articles

14 Dec 2022 : Clinical Research   1,477,232

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

17 Jan 2024 : Review article   1,433,627

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

16 May 2023 : Clinical Research   690,157

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial   50,150

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

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