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Open AccessArticle

Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations

1
CNR-Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”-Unit of Bologna, 40136 Bologna, Italy
2
IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
3
Ortopedia-Traumatologia e Chirurgia Protesica e dei Reimpianti d’Anca e di Ginocchio, Istituto Ortopedico Rizzoli di Bologna, 40136 Bologna, Italy
4
Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali, Università Degli Studi Di Messina, 98122 Messina, Italy
5
Department of Biomedical and Neuromotor Sciences, University of Bologna, 40123 Bologna, Italy
6
Department of Orthopedic and Trauma Surgery, Ospedale Maggiore, 40133 Bologna, Italy
7
st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 409; https://doi.org/10.3390/cells9020409
Received: 20 December 2019 / Revised: 5 February 2020 / Accepted: 7 February 2020 / Published: 11 February 2020
(This article belongs to the Special Issue Extracellular Matrix Remodeling 2019)
Mutations in collagen VI genes cause two major clinical myopathies, Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), and the rarer myosclerosis myopathy. In addition to congenital muscle weakness, patients affected by collagen VI-related myopathies show axial and proximal joint contractures, and distal joint hypermobility, which suggest the involvement of tendon function. To gain further insight into the role of collagen VI in human tendon structure and function, we performed ultrastructural, biochemical, and RT-PCR analysis on tendon biopsies and on cell cultures derived from two patients affected with BM and UCMD. In vitro studies revealed striking alterations in the collagen VI network, associated with disruption of the collagen VI-NG2 (Collagen VI-neural/glial antigen 2) axis and defects in cell polarization and migration. The organization of extracellular matrix (ECM) components, as regards collagens I and XII, was also affected, along with an increase in the active form of metalloproteinase 2 (MMP2). In agreement with the in vitro alterations, tendon biopsies from collagen VI-related myopathy patients displayed striking changes in collagen fibril morphology and cell death. These data point to a critical role of collagen VI in tendon matrix organization and cell behavior. The remodeling of the tendon matrix may contribute to the muscle dysfunction observed in BM and UCMD patients.
Keywords: collagen VI; extracellular matrix remodeling; Ullrich congenital muscular dystrophy; Bethlem myopathy; pericellular matrix; cell polarization; NG2 proteoglycan; metalloproteinase 2; cell-extracellular matrix interactions collagen VI; extracellular matrix remodeling; Ullrich congenital muscular dystrophy; Bethlem myopathy; pericellular matrix; cell polarization; NG2 proteoglycan; metalloproteinase 2; cell-extracellular matrix interactions
MDPI and ACS Style

Antoniel, M.; Traina, F.; Merlini, L.; Andrenacci, D.; Tigani, D.; Santi, S.; Cenni, V.; Sabatelli, P.; Faldini, C.; Squarzoni, S. Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations. Cells 2020, 9, 409.

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