Xylosyltransferase I mediates the synthesis of proteoglycans with long glycosaminoglycan chains and controls chondrocyte hypertrophy and collagen fibers organization of in the growth plate.
Fiche publication
Date publication
juin 2023
Journal
Cell death & disease
Auteurs
Membres identifiés du Cancéropôle Est :
Dr OUZZINE Mohamed
Tous les auteurs :
Taieb M, Ghannoum D, Barré L, Ouzzine M
Lien Pubmed
Résumé
Genetic mutations in the Xylt1 gene are associated with Desbuquois dysplasia type II syndrome characterized by sever prenatal and postnatal short stature. However, the specific role of XylT-I in the growth plate is not completely understood. Here, we show that XylT-I is expressed and critical for the synthesis of proteoglycans in resting and proliferative but not in hypertrophic chondrocytes in the growth plate. We found that loss of XylT-I induces hypertrophic phenotype-like of chondrocytes associated with reduced interterritorial matrix. Mechanistically, deletion of XylT-I impairs the synthesis of long glycosaminoglycan chains leading to the formation of proteoglycans with shorter glycosaminoglycan chains. Histological and Second Harmonic Generation microscopy analysis revealed that deletion of XylT-I accelerated chondrocyte maturation and prevents chondrocytes columnar organization and arrangement in parallel of collagen fibers in the growth plate, suggesting that XylT-I controls chondrocyte maturation and matrix organization. Intriguingly, loss of XylT-I induced at embryonic stage E18.5 the migration of progenitor cells from the perichondrium next to the groove of Ranvier into the central part of epiphysis of E18.5 embryos. These cells characterized by higher expression of glycosaminoglycans exhibit circular organization then undergo hypertrophy and death creating a circular structure at the secondary ossification center location. Our study revealed an uncovered role of XylT-I in the synthesis of proteoglycans and provides evidence that the structure of glycosaminoglycan chains of proteoglycans controls chondrocyte maturation and matrix organization.
Mots clés
Humans, Chondrocytes, metabolism, Proteoglycans, metabolism, Growth Plate, Glycosaminoglycans, Collagen, metabolism, Hypertrophy, metabolism
Référence
Cell Death Dis. 2023 06 9;14(6):355