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Article

Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

1
Functional Proteomics Laboratory, Department of Life Sciences, University of Siena, 53100 Siena, Italy
2
Division of Laboratory Medicine, Department of Medicine, University Medical Center, 1206 Geneva, Switzerland
3
Biochemistry Unit, Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy
4
Istituto Universitario di Studi Superiori-IUSS, 27100 Pavia, Italy
*
Authors to whom correspondence should be addressed.
These Authors contributed equally to the work.
These Authors contributed equally to the work.
§
Current address: Futura Facility Management s.r.l., Strada di Gabbricce, 19/A-53035-Monteriggioni, 53035 Siena, Italy.
Int. J. Mol. Sci. 2021, 22(1), 429; https://doi.org/10.3390/ijms22010429
Received: 1 December 2020 / Revised: 28 December 2020 / Accepted: 29 December 2020 / Published: 4 January 2021
(This article belongs to the Special Issue Proteomics Analysis in Biomarker Discovery)
Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease biomarkers in OI probands with different mutations and lethal or surviving phenotypes, primary fibroblasts from dominant OI patients, carrying COL1A1 or COL1A2 defects, were investigated by applying a Tandem Mass Tag labeling-Liquid Chromatography-Tandem Mass Spectrometry (TMT LC-MS/MS) proteomics approach and bioinformatic tools for comparative protein-abundance profiling. While no difference in α1 or α2 abundance was detected among lethal (type II) and not-lethal (type III) OI patients, 17 proteins, with key effects on matrix structure and organization, cell signaling, and cell and tissue development and differentiation, were significantly different between type II and type III OI patients. Among them, some non–collagenous extracellular matrix (ECM) proteins (e.g., decorin and fibrillin-1) and proteins modulating cytoskeleton (e.g., nestin and palladin) directly correlate to the severity of the disease. Their defective presence may define proband-failure in balancing aberrances related to mutant collagen. View Full-Text
Keywords: osteogenesis imperfecta; extracellular matrix; cytoskeleton; cell signaling; bioinformatics; REVIGO; pathway analysis osteogenesis imperfecta; extracellular matrix; cytoskeleton; cell signaling; bioinformatics; REVIGO; pathway analysis
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MDPI and ACS Style

Bini, L.; Schvartz, D.; Carnemolla, C.; Besio, R.; Garibaldi, N.; Sanchez, J.-C.; Forlino, A.; Bianchi, L. Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach. Int. J. Mol. Sci. 2021, 22, 429. https://doi.org/10.3390/ijms22010429

AMA Style

Bini L, Schvartz D, Carnemolla C, Besio R, Garibaldi N, Sanchez J-C, Forlino A, Bianchi L. Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach. International Journal of Molecular Sciences. 2021; 22(1):429. https://doi.org/10.3390/ijms22010429

Chicago/Turabian Style

Bini, Luca, Domitille Schvartz, Chiara Carnemolla, Roberta Besio, Nadia Garibaldi, Jean-Charles Sanchez, Antonella Forlino, and Laura Bianchi. 2021. "Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach" International Journal of Molecular Sciences 22, no. 1: 429. https://doi.org/10.3390/ijms22010429

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