Glycans modify mesenchymal stem cell differentiation to impact on the function of resulting osteoblasts

Wilson, K. M., Jagger, A. M., Walker, M. , Seinkmane, E., Fox, J. M., Kröger, R., Genever, P. and Ungar, D. (2018) Glycans modify mesenchymal stem cell differentiation to impact on the function of resulting osteoblasts. Journal of Cell Science, 131(4), jcs209452. (doi:10.1242/jcs.209452) (PMID:29361539) (PMCID:PMC5868951)

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Abstract

Glycans are inherently heterogeneous, yet glycosylation is essential in eukaryotes, and glycans show characteristic cell type-dependent distributions. By using an immortalized human mesenchymal stromal cell (MSC) line model, we show that both N- and O-glycan processing in the Golgi functionally modulates early steps of osteogenic differentiation. We found that inhibiting O-glycan processing in the Golgi prior to the start of osteogenesis inhibited the mineralization capacity of the formed osteoblasts 3 weeks later. In contrast, inhibition of N-glycan processing in MSCs altered differentiation to enhance the mineralization capacity of the osteoblasts. The effect of N-glycans on MSC differentiation was mediated by the phosphoinositide-3-kinase (PI3K)/Akt pathway owing to reduced Akt phosphorylation. Interestingly, by inhibiting PI3K during the first 2 days of osteogenesis, we were able to phenocopy the effect of inhibiting N-glycan processing. Thus, glycan processing provides another layer of regulation that can modulate the functional outcome of differentiation. Glycan processing can thereby offer a novel set of targets for many therapeutically attractive processes.

Item Type:Articles
Additional Information:This work was supported by an Engineering and Physical Sciences Research Council-funded studentship (supporting K.M.W.) awarded to P.G. and D.U., and by the Arthritis Research UK Tissue Engineering Centre (19429).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Walker, Mr Matthew
Authors: Wilson, K. M., Jagger, A. M., Walker, M., Seinkmane, E., Fox, J. M., Kröger, R., Genever, P., and Ungar, D.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Journal of Cell Science
Publisher:Company of Biologists
ISSN:0021-9533
ISSN (Online):1477-9137
Published Online:11 January 2018
Copyright Holders:Copyright © 2018 The Company of Biologists Ltd
First Published:First published in Journal of Cell Science 131(4): jcs209452
Publisher Policy:Reproduced under a Creative Commons License

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