P135 - Core-fucosylation Deficiency Inhibits Recovery in Early Degenerative Cartilage
- K. Homan (Sapporo, JP)
- K. Homan (Sapporo, JP)
- T. Onodera (Sapporo, JP)
- H. Hanamatsu (Sapporo, JP)
- J. Furukawa (Sapporo, JP)
- T. Miyazaki (sapporo, JP)
- J. Yamaguchi (Sapporo, JP)
- Y. Hosokawa (Sapporo, JP)
- T. Ebata (Sapporo, JP)
- D. Liang (Sapporo, JP)
- W. Kim (Sapporo, JP)
- M. Matsuoka (Sapporo, JP)
- N. Iwasaki (Sapporo, JP)
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.