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Madindoline A Affects the Osteogenic Potential and the Wnt Signaling

Journal article
Authors Anna Thorfve
Emilia Svala
Helena Brisby
Peter Thomsen
Anders Lindahl
Pentti Tengvall
Published in Journal of Bone Marrow Research
Volume 2
Issue 3
Pages 1000151
ISSN 2329-8820
Publication year 2014
Published at Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Institute of Clinical Sciences, Department of Biomaterials
Institute of Clinical Sciences, Department of Orthopaedics
Pages 1000151
Language en
Links esciencecentral.org/journals/madind...
Keywords IL-6 inhibitor; Madindoline A; Osteogenic differentiation;
Subject categories Medical Biotechnology, Medical Engineering, Materials Engineering, Biological Sciences

Abstract

Background: Human mesenchymal stem cells (hMSCs) have the potential to differentiate at least into adipocytes, chondrocytes and osteoblasts. The differentiation capacity can be modulated by drugs, or chemical substances that affect diverse mechanisms essential for e.g. bone formation. The aim of this study was to investigate the osteoinductive capacity of the interleukin-6 (IL-6) inhibitor Madindoline A (MadA) and its relation to the bone-inducing Wnt signaling pathways. Methods: After stimulation with MadA of hMSC from 4 donors (aged 13-33 years) in an in vitro culture, alkaline phosphatase (ALP) activity and extracellular matrix (ECM) mineralization of hMSCs were quantified and calcification visualized by von Kossa staining. The expression of bone- and Wnt related markers was further studied at gene and protein levels. In addition, stimulation with the non-canonical Wnt5a ligand was added as a positive control, and the effect of MadA on IL-6 gene expression and STAT3 phosphorylation was evaluated. Results: Stimulation with MadA induced increased ECM mineralization and upregulated the expression of the bone related genes RUNX2, COL1A1 and Osteocalcin, although large donor-to-donor differences were observed. Further, MadA affected both the canonical and non-canonical Wnt signaling pathways and displayed a superior osteoinducing property compared to Wnt5a in some cases. Conclusion: In summary, all donors displayed higher gene expression of IL-6 and reduced STAT3 phosphorylation after MadA stimulation. The present results provide for the first time indications of an in vitro osteoinduction potential of the IL-6 inhibitor MadA.

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