Madindoline A Affects the Osteogenic Potential and the Wnt Signaling Pathways during Osteogenic Differentiation of Human Mesenchymal Stem Cells in vitro

作者: A Thorfve , E Svala , H Brisby , P Thomsen , A Lindahl

DOI: 10.4172/2329-8820.1000151

关键词:

摘要: 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. aim of this study was investigate osteoinductive interleukin-6 (IL-6) inhibitor Madindoline A (MadA) its relation bone-inducing Wnt signaling pathways. Methods: After stimulation with MadA hMSC from 4 donors (aged 13-33 years) in an vitro culture, alkaline phosphatase (ALP) activity extracellular matrix (ECM) mineralization hMSCs were quantified calcification visualized von Kossa staining. expression bone- related markers further studied gene protein levels. In addition, non-canonical Wnt5a ligand added as a positive control, effect on IL-6 STAT3 phosphorylation evaluated. Results: Stimulation induced increased ECM upregulated genes RUNX2, COL1A1 Osteocalcin, although large donor-to-donor differences observed. Further, affected both canonical pathways displayed superior osteoinducing property compared some cases. Conclusion: summary, all higher reduced after stimulation. present results provide first time indications osteoinduction MadA.

参考文章(54)
Peter C. HEINRICH, Iris BEHRMANN, Gerhard MÜLLER-NEWEN, Fred SCHAPER, Lutz GRAEVE, INTERLEUKIN-6-TYPE CYTOKINE SIGNALLING THROUGH THE GP130/JAK/STAT PATHWAY Biochemical Journal. ,vol. 334, pp. 297- 314 ,(1998) , 10.1042/BJ3340297
David G. Monroe, Meghan E. McGee-Lawrence, Merry Jo Oursler, Jennifer J. Westendorf, Update on Wnt signaling in bone cell biology and bone disease Gene. ,vol. 492, pp. 1- 18 ,(2012) , 10.1016/J.GENE.2011.10.044
Renée van Amerongen, Christophe Fuerer, Makiko Mizutani, Roel Nusse, Wnt5a can both activate and repress Wnt/β-catenin signaling during mouse embryonic development Developmental Biology. ,vol. 369, pp. 101- 114 ,(2012) , 10.1016/J.YDBIO.2012.06.020
Masanori Okamoto, Nobuyuki Udagawa, Shunsuke Uehara, Kazuhiro Maeda, Teruhito Yamashita, Yuko Nakamichi, Hiroyuki Kato, Naoto Saito, Yasuhiro Minami, Naoyuki Takahashi, Yasuhiro Kobayashi, Noncanonical Wnt5a enhances Wnt/β-catenin signaling during osteoblastogenesis. Scientific Reports. ,vol. 4, pp. 4493- 4493 ,(2015) , 10.1038/SREP04493
Christoph Garbers, Jürgen Scheller, Interleukin-6 and interleukin-11: same same but different. Biological Chemistry. ,vol. 394, pp. 1145- 1161 ,(2013) , 10.1515/HSZ-2013-0166
Eiji Nemoto, Yukari Ebe, Sousuke Kanaya, Masahiro Tsuchiya, Takashi Nakamura, Masato Tamura, Hidetoshi Shimauchi, Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis. Biochemical and Biophysical Research Communications. ,vol. 422, pp. 627- 632 ,(2012) , 10.1016/J.BBRC.2012.05.039
Yan Liu, Boris Rubin, Peter V.N. Bodine, Julia Billiard, Wnt5a induces homodimerization and activation of Ror2 receptor tyrosine kinase. Journal of Cellular Biochemistry. ,vol. 105, pp. 497- 502 ,(2008) , 10.1002/JCB.21848
Verena Dexheimer, Sebastian Mueller, Frank Braatz, Wiltrud Richter, Reduced Reactivation from Dormancy but Maintained Lineage Choice of Human Mesenchymal Stem Cells with Donor Age PLoS ONE. ,vol. 6, pp. e22980- ,(2011) , 10.1371/JOURNAL.PONE.0022980
Vincenzo Desiderio, Virginia Tirino, Gianpaolo Papaccio, Francesca Paino, Bone defects: Molecular and cellular therapeutic targets The International Journal of Biochemistry & Cell Biology. ,vol. 51, pp. 75- 78 ,(2014) , 10.1016/J.BIOCEL.2014.03.025
Atsuo Adachi, Tomosaburo Takahashi, Takehiro Ogata, Hiroko Imoto-Tsubakimoto, Naohiko Nakanishi, Tomomi Ueyama, Hiroaki Matsubara, NFAT5 regulates the canonical Wnt pathway and is required for cardiomyogenic differentiation. Biochemical and Biophysical Research Communications. ,vol. 426, pp. 317- 323 ,(2012) , 10.1016/J.BBRC.2012.08.069