title: Depletion of Gangliosides Enhances Articular Cartilage Repair in Mice.
abstract: Elucidation of the healing mechanisms in damaged tissues is a critical step for establishing breakthroughs in tissue engineering. Articular cartilage is clinically one of the most successful tissues to be repaired with regenerative medicine because of its homogeneous extracellular matrix and few cell types. However, we only poorly understand cartilage repair mechanisms, and hence, regenerated cartilage remains inferior to the native tissues. Here, we show that glycosylation is an important process for hypertrophic differentiation during articular cartilage repair. GM3, which is a precursor molecule for most gangliosides, was transiently expressed in surrounding damaged tissue, and depletion of GM3 synthase enhanced cartilage repair. Gangliosides also regulated chondrocyte hypertrophy via the Indian hedgehog pathway. These results identify a novel mechanism of cartilage healing through chondrocyte hypertrophy that is regulated by glycosylation. Manipulation of gangliosides and their synthases may have beneficial effects on articular cartilage repair.
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Matsuoka
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Onodera
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Homan
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Sasazawa
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Furukawa
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Momma
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Rikiya
authors.initials: R
authors.lastname: Baba
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Hontani
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Zenta
authors.initials: Z
authors.lastname: Joutoku
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Laboratory of Biochemistry, Azabu University, Graduate School of Veterinary Medicine, Sagamihara, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D015415:Biomarkers; D001861:Bone Regeneration; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005679:G(M3) Ganglioside / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D023822:Tissue Engineering; D014945:Wound Healing / Q000235:genetics
chemical_list: D015415:Biomarkers; D005679:G(M3) Ganglioside; D005732:Gangliosides; D053823:Hedgehog Proteins; C514061:ihh protein, mouse; D003094:Collagen