K. Homan (Sapporo, JP)
Hokkaido University Orthopaedic SurgeryPresenter Of 1 Presentation
P135 - Core-fucosylation Deficiency Inhibits Recovery in Early Degenerative Cartilage
Abstract
Purpose
High-mannose (HM) type N-glycans are known to decrease earlier than histological degeneration and artificial depletion of these glycans causes cartilage degeneration as well as fucosylation of N-glycans (Urita, Homan). However, the effect of fucosylation of N-glycans on cartilage degradation has not been clarified. The purpose of this study was to analyze the effects of fucosyltransferase (α1,6-fucosyltransferase: FUT8) deletion on OA progression.
Methods and Materials
Mice with FUT8 deletion in cartilage-specific type II collagen-expressing cells were generated by crossing mice carrying the fut8 floxed allele to Tg(Col2a1-Cre) mice. Mice were followed for the spontaneous development of OA up to 15 months of age. The femoral head cartilage was cultured for 72 h in serum-free DMEM-plus α-mannosidase. After stimulation, they were returned to complete medium and their recovery from cartilage degeneration was assessed. The expression mode of FUT8 in mouse cartilage N-glycans was confirmed using MALDI-TOF/MS-based high-throughput structural profiling (glycoblotting method).
Results
Cartilage degeneration progressed earlier in aging models of FUT8-deficient mice than in control mice (wild-type and floxed mice) (Figure 1). Enzymatic degradation of HM-glycan on the cartilage in FUT8-deficient mice exacerbated cartilage degeneration. Furthermore, histological cartilage repair after enzyme removal was seen in the control cartilage, but not in FUT8-deficient cartilage. (Figure 2).
Conclusion
Reduction of HM-glycans in cartilage induced early OA-like degeneration, leading to core-fucosylation of N-glycans. Reversible cartilage degeneration caused by adding α-mannosidase was found to transition to irreversible degeneration by inhibiting the core-fucosylation of N-glycan. These results indicate that the core-fucosylation of glycan structures may be involved in reversible tissue repair in the early stages of cartilage degeneration, and the pathogenesis of early degeneration contributes to the development of OA.
Presenter Of 1 Presentation
P135 - Core-fucosylation Deficiency Inhibits Recovery in Early Degenerative Cartilage
Abstract
Purpose
High-mannose (HM) type N-glycans are known to decrease earlier than histological degeneration and artificial depletion of these glycans causes cartilage degeneration as well as fucosylation of N-glycans (Urita, Homan). However, the effect of fucosylation of N-glycans on cartilage degradation has not been clarified. The purpose of this study was to analyze the effects of fucosyltransferase (α1,6-fucosyltransferase: FUT8) deletion on OA progression.
Methods and Materials
Mice with FUT8 deletion in cartilage-specific type II collagen-expressing cells were generated by crossing mice carrying the fut8 floxed allele to Tg(Col2a1-Cre) mice. Mice were followed for the spontaneous development of OA up to 15 months of age. The femoral head cartilage was cultured for 72 h in serum-free DMEM-plus α-mannosidase. After stimulation, they were returned to complete medium and their recovery from cartilage degeneration was assessed. The expression mode of FUT8 in mouse cartilage N-glycans was confirmed using MALDI-TOF/MS-based high-throughput structural profiling (glycoblotting method).
Results
Cartilage degeneration progressed earlier in aging models of FUT8-deficient mice than in control mice (wild-type and floxed mice) (Figure 1). Enzymatic degradation of HM-glycan on the cartilage in FUT8-deficient mice exacerbated cartilage degeneration. Furthermore, histological cartilage repair after enzyme removal was seen in the control cartilage, but not in FUT8-deficient cartilage. (Figure 2).
Conclusion
Reduction of HM-glycans in cartilage induced early OA-like degeneration, leading to core-fucosylation of N-glycans. Reversible cartilage degeneration caused by adding α-mannosidase was found to transition to irreversible degeneration by inhibiting the core-fucosylation of N-glycan. These results indicate that the core-fucosylation of glycan structures may be involved in reversible tissue repair in the early stages of cartilage degeneration, and the pathogenesis of early degeneration contributes to the development of OA.