Morquio A Syndrome: Identification of Differential Patterns of Molecular Pathway Interactions in Bone Lesions

• Published in: International journal of molecular sciences Vol. 25; no. 6; p. 3232
• Main Authors: Álvarez, J Victor, Bravo, Susana B, Chantada-Vázquez, María Pilar, Pena, Carmen, Colón, Cristóbal, Tomatsu, Shunji, Otero-Espinar, Francisco J, Couce, María L
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2024; MDPI
• Subjects: Adenosine triphosphate; animal studies; Animals; Apoptosis; Arthritis; biomarkers; Bone Diseases; Bones; Cartilage; Cartilage Diseases; Chondroitinsulfatases - genetics; Comparative analysis; Disease; DNA damage; Energy; Enzymes; Extracellular matrix; Humans; Medical research; Medicine, Experimental; Metabolism; Mice; Mice, Knockout; Mitochondria; Mucopolysaccharidosis IV - metabolism; mucopolysaccharidosis type IV; musculoskeletal manifestations; Oxidation; Oxidative stress; Phosphorylation; Proteins; proteomic; Ribonucleic acid; RNA; Spinal cord; Sulfates; Spain; mucopolysaccharidosis type IV; proteomic; animal studies; musculoskeletal manifestations; biomarkers
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25063232

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice (UNT) to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.