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Collagen transport and related pathways in Osteogenesis Imperfecta.
- Source :
-
Human genetics [Hum Genet] 2021 Aug; Vol. 140 (8), pp. 1121-1141. Date of Electronic Publication: 2021 Jun 24. - Publication Year :
- 2021
-
Abstract
- Osteogenesis Imperfecta (OI) comprises a heterogeneous group of patients who share bone fragility and deformities as the main characteristics, albeit with different degrees of severity. Phenotypic variation also exists in other connective tissue aspects of the disease, complicating disease classification and disease course prediction. Although collagen type I defects are long established as the primary cause of the bone pathology, we are still far from comprehending the complete mechanism. In the last years, the advent of next generation sequencing has triggered the discovery of many new genetic causes for OI, helping to draw its molecular landscape. It has become clear that, in addition to collagen type I genes, OI can be caused by multiple proteins connected to different parts of collagen biosynthesis. The production of collagen entails a complex process, starting from the production of the collagen Iα1 and collagen Iα2 chains in the endoplasmic reticulum, during and after which procollagen is subjected to a plethora of posttranslational modifications by chaperones. After reaching the Golgi organelle, procollagen is destined to the extracellular matrix where it forms collagen fibrils. Recently discovered mutations in components of the retrograde transport of chaperones highlight its emerging role as critical contributor of OI development. This review offers an overview of collagen regulation in the context of recent gene discoveries, emphasizing the significance of transport disruptions in the OI mechanism. We aim to motivate exploration of skeletal fragility in OI from the perspective of these pathways to identify regulatory points which can hint to therapeutic targets.
- Subjects :
- Bone and Bones pathology
Collagen Type I genetics
Endoplasmic Reticulum genetics
Endoplasmic Reticulum metabolism
Extracellular Matrix chemistry
Extracellular Matrix metabolism
Golgi Apparatus genetics
Golgi Apparatus metabolism
High-Throughput Nucleotide Sequencing
Humans
Molecular Chaperones genetics
Molecular Chaperones metabolism
Mutation
Osteoblasts pathology
Osteogenesis Imperfecta genetics
Osteogenesis Imperfecta pathology
Procollagen genetics
Protein Biosynthesis
Protein Isoforms biosynthesis
Protein Isoforms genetics
Protein Transport
Severity of Illness Index
Bone and Bones metabolism
Collagen Type I biosynthesis
Osteoblasts metabolism
Osteogenesis Imperfecta metabolism
Procollagen biosynthesis
Protein Processing, Post-Translational
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1203
- Volume :
- 140
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 34169326
- Full Text :
- https://doi.org/10.1007/s00439-021-02302-2