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)

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, Dr 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