Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics

Hopkinson, M; Pitsillides, AA

Abstract

Contributions made by the dystrophin-associated glycoprotein complex (DGC) to cell-cell and cell-extracellular matrix (ECM) interactions are vital in development, homeostasis and pathobiology. This review explores how DGC functions may extend to skeletal pathophysiology by appraising the known roles of its major ECM ligands, and likely associated DGC signalling pathways, in regulating cartilage and bone cell behaviour and emergent skeletal phenotypes. These considerations will be contextualised by highlighting the potential of studies into the role of the DGC in isolated chondrocytes, osteoblasts and osteoclasts, and by fuller deliberation of skeletal phenotypes that may emerge in very young mice lacking vital, yet diverse core elements of the DGC. Our review points to roles for individual DGC components-including the glycosylation of dystroglycan itself-beyond the establishment of membrane stability which clearly accounts for severe muscle phenotypes in muscular dystrophy. It implies that the short stature, low bone mineral density, poor bone health and greater fracture risk in these patients, which has been attributed due to primary deficiencies in muscle-evoked skeletal loading, may instead arise due to primary roles for the DGC in controlling skeletal tissue (re)modelling.

Citation

Hopkinson, M., & Pitsillides, A. (2025). Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics. International Journal of Experimental Pathology, 106(2), https://doi.org/10.1111/iep.12525

• Journal Article Type: Article
• Acceptance Date: Dec 29, 2024
• Online Publication Date: Feb 8, 2025
• Publication Date: 2025
• Deposit Date: Mar 10, 2025
• Publicly Available Date: Mar 10, 2025
• Print ISSN: 0959-9673
• Electronic ISSN: 1365-2613
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 106
• Issue: 2
• DOI: https://doi.org/10.1111/iep.12525
• Keywords: bone; cartilage; dystrophin associated glycoprotein complex; extracellular matrix; skeletal; DUCHENNE MUSCULAR-DYSTROPHY; FUKUTIN-RELATED PROTEIN; MESENCHYMAL STEM-CELL; ENHANCES OSTEOGENIC DIFFERENTIATION; HEPARAN-SULFATE PROTEOGLYCAN; HIPPO SIGNALING-PATHWAY; OSTEOBLAST-LIKE CELLS; COLLAGEN TYPE-IV; MEK-ERK PATHWAY; PERICELLULAR MATRIX