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

TY - JOUR

T1 - Glycans modify mesenchymal stem cell differentiation to impact on the function of resulting osteoblasts

AU - Wilson, Katherine M.

AU - Jagger, Alistair M

AU - Walker, Matthew

AU - Seinkmane, Estere

AU - Fox, James M.

AU - Kröger, Roland

AU - Genever, Paul

AU - Ungar, Daniel

N1 - © 2018. Published by The Company of Biologists Ltd. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2018/2/14

Y1 - 2018/2/14

N2 - 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.

AB - 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.

KW - Glycan processing

KW - Hydroxyapatite

KW - Kifunensine

KW - Osteogenesis

KW - PI3K signalling

UR - http://www.scopus.com/inward/record.url?scp=85042415509&partnerID=8YFLogxK

U2 - 10.1242/jcs.209452

DO - 10.1242/jcs.209452

M3 - Article

C2 - 29361539

SN - 0021-9533

VL - 131

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - 4

M1 - jcs209452

ER -