Format

Send to

Choose Destination
See comment in PubMed Commons below
Exp Cell Res. 2017 Nov 15;360(2):413-420. doi: 10.1016/j.yexcr.2017.09.034. Epub 2017 Sep 27.

Glycosylation status of bone sialoprotein and its role in mineralization.

Author information

1
Department of Biochemistry and Molecular Biology, Soochow University Medical College, Suzhou 215123, China. Electronic address: xulan@suda.edu.cn.
2
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. Electronic address: z_zhang@suda.edu.cn.
3
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
4
Department of Biochemistry and Molecular Biology, Soochow University Medical College, Suzhou 215123, China.
5
Department of Orthopaedic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
6
Shanghai Green-Valley Pharmaceutical Co. Ltd., Shanghai 201200, China.

Abstract

The highly glycosylated bone sialoprotein (BSP) is an abundant non-collagenous phosphoprotein in bone which enhances osteoblast differentiation and new bone deposition in vitro and in vivo. However, the structural details of its different glycosylation linkages have not been well studied and their functions in bone homeostasis are not clear. Previous studies suggested that the O-glycans, but not the N-glycans on BSP, are highly sialylated. Herein, we employed tandem mass spectrometry (MS/MS) to demonstrate that the N-glycanson the recombinant human integrin binding sialoprotein (rhiBSP) are also enriched in sialic acids (SAs) at their termini. We also identified multiple novel sites of N-glycan modification. Treatment of rhiBSP enhances osteoblast differentiation and mineralization of MC3T3-E1 cells and this effect could be partially reversed by efficient enzymatic removal of its N-glycans. Removal of all terminal SAs has a greater effect in reversing the effect of rhiBSP on osteogenesis, especially on mineralization, suggesting that sialylation at the termini of both N-glycans and O-glycans plays an important role in this regulation. Moreover, BSP-conjugated SAs may affect mineralization via ERK activation of VDR expression. Collectively, our results identified novel N-glycans enriched in SAs on the rhiBSP and demonstrated that SAs at both N- and O-glycans are important for BSP regulation of osteoblast differentiation and mineralization in vitro.

KEYWORDS:

Bone sialoprotein; Glycans; Mass spectrometry; Mineralization; Sialic acids

PMID:
28958711
DOI:
10.1016/j.yexcr.2017.09.034
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center