Mutations in the collagen VI gene cause two major clinical myopathies – Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), and the rarer myosclerosis myopathy. Patients affected by collagen VI-related myopathies elicit:

• Congenital muscle weakness;
• Axial and proximal joint contractures; and
• Distal joint hypermobility – indicating the involvement of tendon function.

The goal of a new study published in Cells was to gain further insight into the role of collagen VI in human tendon structure and function. This study entailed an 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 showed 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. In addition, the organization of extracellular matrix (ECM) components—with regard to collagens I and XII—was also affected, along with an increase in the active form of metalloproteinase 2 (MMP2). While results of tendon biopsies from collagen VI-related myopathy patients displayed striking changes in collagen fibril morphology and cell death. The findings indicated a critical role of collagen VI in tendon matrix organization and cell behavior. It was stated that the remodeling of tendon matrix may contribute to the muscle dysfunction observed in BM and UCMD patients.

Source: Cells. 2020 Feb 11;9(2). pii: E409. doi: 10.3390/cells9020409.