Abstract
C-type natriuretic peptide (CNP) signaling has been implicated as an important regulator of chondrogenic differentiation during endochondral bone development. This preliminary study further investigated the putative effectors and/or targets of CNP signaling in transforming growth factor (TGF)-β induced in vitro chondrogenic differentiation of mesenchymal stem cells (MSCs). Previously characterized human trabecular bone derived MSCs were induced either with only TGF-β1 or with a combination of TGF-β1 and CNP in micromass culture for 10 or 20 days. Genome wide gene expression profile changes in between these two groups were analyzed on day-10 or day-20 of culture. Results revealed that there were only 7 genes, whose expression change was fourfolds or higher in TGF-β1 and CNP fed group in comparison to only TGF-β1 fed group. The up-regulated genes included matrilin-3 (MATN3), engulfment and cell motility 1 (ELMO1), CD24, and DCN1, defective in cullin neddylation 1, domain containing 1 (DCUN1D1). The down-regulated genes, on the other hand, included LIM domain kinase 2 (LIMK2), Ewing sarcoma breakpoint region 1, and guanine nucleotide binding protein (G protein), gamma 12 (GNG12). The up-regulation of MATN3 was confirmed on the basis of RT-PCR. The known literature on both CNP signaling and MATN3 function in chondrogenesis match with each other and suggest MATN3 as a putative effector and/or target of CNP signaling during this process.
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Acknowledgments
This work was supported by funding from TUBITAK, The Scientific and Technological Research Council of Turkey (Grant: SBAG-108S189). Authors thank Professor Hilal Ozdag, from Biotechnology Institute, Ankara University, Ankara, Turkey, for her generous guidance in microarray preprocessing, quality control, differentially expressed gene set analyses, sample based clustering analyses, and bioinformatics.
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Mustafa Ege Babadagli participated as a voluntary summer student in this study.
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Babadagli, M.E., Tezcan, B., Yilmaz, S.T. et al. Matrilin-3 as a putative effector of C-type natriuretic peptide signaling during TGF-β induced chondrogenic differentiation of mesenchymal stem cells. Mol Biol Rep 41, 5549–5555 (2014). https://doi.org/10.1007/s11033-014-3448-3
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DOI: https://doi.org/10.1007/s11033-014-3448-3