title: Effect of mechanical strain on the collagen VI pericellular matrix in anterior cruciate ligament fibroblasts.
abstract: Cell-extracellular matrix interaction plays a major role in maintaining the structural integrity of connective tissues and sensing changes in the biomechanical environment of cells. Collagen VI is a widely expressed non-fibrillar collagen, which regulates tissues homeostasis. The objective of the present investigation was to extend our understanding of the role of collagen VI in human ACL. This study shows that collagen VI is associated both in vivo and in vitro to the cell membrane of knee ACL fibroblasts, contributing to the constitution of a microfibrillar pericellular matrix. In cultured cells the localization of collagen VI at the cell surface correlated with the expression of NG2 proteoglycan, a major collagen VI receptor. The treatment of ACL fibroblasts with anti-NG2 antibody abolished the localization of collagen VI indicating that collagen VI pericellular matrix organization in ACL fibroblasts is mainly mediated by NG2 proteoglycan. In vitro mechanical strain injury dramatically reduced the NG2 proteoglycan protein level, impaired the association of collagen VI to the cell surface, and promoted cell cycle withdrawal. Our data suggest that the injury-induced alteration of specific cell-ECM interactions may lead to a defective fibroblast self-renewal and contribute to the poor regenerative ability of ACL fibroblasts.
authors.affiliation: National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy; IOR-IRCCS, SC Laboratory of Musculoskeletal Cell Biology, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sardone
authors.forename: Francesco
authors.initials: F
authors.lastname: Traina
authors.forename: Francesca
authors.initials: F
authors.lastname: Tagliavini
authors.forename: Camilla
authors.initials: C
authors.lastname: Pellegrini
authors.forename: Luciano
authors.initials: L
authors.lastname: Merlini
authors.forename: Stefano
authors.initials: S
authors.lastname: Squarzoni
authors.forename: Spartaco
authors.initials: S
authors.lastname: Santi
authors.forename: Simona
authors.initials: S
authors.lastname: Neri
authors.forename: Cesare
authors.initials: C
authors.lastname: Faldini
authors.forename: Nadir
authors.initials: N
authors.lastname: Maraldi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sabatelli
mesh_terms: D016118:Anterior Cruciate Ligament / Q000378:metabolism* / Q000648:ultrastructure; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D024142:Collagen Type VI / Q000378:metabolism* / Q000648:ultrastructure; D003238:Connective Tissue / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D013314:Stress, Mechanical
chemical_list: D024142:Collagen Type VI; D016326:Extracellular Matrix Proteins