Related Experiment Video
Updated: Jan 8, 2026
08:51
Profiling of Permethylated Mucin O-glycans Using Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry
Published on: June 20, 2025
534
Mucin-type O-glycans regulate proteoglycan stability and chondrocyte maturation
Xiaolin Dong1,2, Sydney Bedillion1,2, Kaleigh E Gosnell2
1Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.
Biorxiv : the Preprint Server for Biology
|December 19, 2025
Summary
Extended O-glycans and heparan sulfate proteoglycans (HSPGs) functionally interact. Loss of O-glycans impairs proteoglycan stability and chondrogenesis, revealing new glycosylation roles in development and disease.
Area of Science:
- Biochemistry
- Cell Biology
- Developmental Biology
Background:
- O-glycosylation is a vital post-translational modification impacting protein function and tissue development.
- The precise roles of distinct O-glycan subclasses in coordinating tissue development are not fully understood.
- Heparan sulfate proteoglycans (HSPGs) are critical regulators of cell signaling and tissue organization.
Purpose of the Study:
- To investigate the functional crosstalk between extended mucin-type O-glycans and HSPGs.
- To elucidate the impact of O-glycan deficiency on cell signaling and extracellular matrix remodeling.
- To understand the role of O-glycans in chondrogenesis and their contribution to glycosylation disorders.
Main Methods:
- Genetic ablation of C1GALT1 and COSMC in human chondrocytes.
- Analysis of cell surface HSPG levels and fibroblast growth factor (FGF) binding.
- Transcriptomic and secretome analyses.
- Assessment of Syndecan-1 and CD44v3 expression and function.
- Evaluation of chondrogenesis in growth plate-like chondroprogenitors.
Main Results:
- Genetic deficiency in O-glycosylation (C1GALT1 or COSMC) reduced cell surface HSPGs and FGF binding.
- Impaired MAPK/ERK signaling and disrupted chondrogenesis were observed in deficient cells.
- Truncation of O-GalNAc glycans led to decreased Syndecan-1 levels and diminished CD44v3-mediated FGF1 binding.
- Extracellular matrix remodeling and selective loss of proteoglycan expression occurred in deficient cells.
Conclusions:
- Extended mucin-type O-glycans are crucial for maintaining proteoglycan stability and function.
- Functional crosstalk between O-glycans and HSPGs is essential for normal chondrogenesis.
- These findings highlight cross-regulatory glycosylation mechanisms vital for development and relevant to glycosylation-related disorders.
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