From collagen denaturation caused by a COL1A2 variant to mineral disorganization and tubular occlusion in primary dentin with dentinogenesis imperfecta
Abstract
Dentinogenesis Imperfecta (DI) is a rare genetic disorder that disrupts the structure and mechanical integrity of dentin, often through alterations to the collagen matrix. In cases associated with Osteogenesis Imperfecta, DI arises from COL1A1 or COL1A2 variants (DI type I). The multiscale mechanisms linking alterations of the collagenic scaffold to dentin microstructural defects remain poorly understood. In this proof-of-concept study, we employed a multimodal 3D characterization framework combining biochemical assays and advanced imaging techniques to investigate the relationship between collagen integrity, mineral organization, and microstructural defects in four (n=4) primary teeth from a DI patient carrying a COL1A2 variant (c.982G>A (p.Gly328Ser)) and eight (n=8) primary teeth from healthy donors. A threefold increase in molecular-level collagen uncoiling (i.e., denaturation) was found in DI dentin compared to healthy dentin using trypsin–hydroxyproline assays. A reduction in the second harmonic generation signal combined with increased spatial variability were observed, indicating pronounced heterogeneities in the collagen scaffold. These heterogeneities were spatially associated with disorganization of the mineral phase, the emergence of hypermineralized regions, and a 30% higher mean mineral density, as measured by high-resolution micro-computed tomography. Severe disruption and partial occlusion of the tubular network were further identified using confocal microscopy, resulting in reduced porosity. These results support a multiscale association between collagen alterations, mineral heterogeneity, and pore network disruption, consistent with a model in which compromised collagen integrity alters the mineral organization and the tubular network of dentin. Although requiring confirmation on larger cohorts, these findings provide a preliminary mechanistic framework for understanding how disruptions of the hierarchical structure of DI dentin, impairing its toughness, may originate from molecular collagen denaturation.
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BibTeX
@article{touraivane2026from,
title = {{From collagen denaturation caused by a COL1A2 variant to mineral disorganization and tubular occlusion in primary dentin with dentinogenesis imperfecta}},
author = {Shangaya Touraivane and Margot Charlotte Riou and William Woolley and Muriel de la Dure-Molla and Benjamin P.J. Fournier and Elsa Vennat and Claire Acevedo},
journal = {Acta Biomaterialia},
year = {2026},
month = oct,
doi = {10.1016/j.actbio.2026.07.021},
url = {https://hal.science/hal-05835720v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - From collagen denaturation caused by a COL1A2 variant to mineral disorganization and tubular occlusion in primary dentin with dentinogenesis imperfecta
AU - Shangaya Touraivane
AU - Margot Charlotte Riou
AU - William Woolley
AU - Muriel de la Dure-Molla
AU - Benjamin P.J. Fournier
AU - Elsa Vennat
AU - Claire Acevedo
PY - 2026
DA - 2026/10/22
JO - Acta Biomaterialia
DO - 10.1016/j.actbio.2026.07.021
UR - https://hal.science/hal-05835720v1
AB - Dentinogenesis Imperfecta (DI) is a rare genetic disorder that disrupts the structure and mechanical integrity of dentin, often through alterations to the collagen matrix. In cases associated with Osteogenesis Imperfecta, DI arises from COL1A1 or COL1A2 variants (DI type I). The multiscale mechanisms linking alterations of the collagenic scaffold to dentin microstructural defects remain poorly understood. In this proof-of-concept study, we employed a multimodal 3D characterization framework combining biochemical assays and advanced imaging techniques to investigate the relationship between collagen integrity, mineral organization, and microstructural defects in four (n=4) primary teeth from a DI patient carrying a COL1A2 variant (c.982G>A (p.Gly328Ser)) and eight (n=8) primary teeth from healthy donors. A threefold increase in molecular-level collagen uncoiling (i.e., denaturation) was found in DI dentin compared to healthy dentin using trypsin–hydroxyproline assays. A reduction in the second harmonic generation signal combined with increased spatial variability were observed, indicating pronounced heterogeneities in the collagen scaffold. These heterogeneities were spatially associated with disorganization of the mineral phase, the emergence of hypermineralized regions, and a 30% higher mean mineral density, as measured by high-resolution micro-computed tomography. Severe disruption and partial occlusion of the tubular network were further identified using confocal microscopy, resulting in reduced porosity. These results support a multiscale association between collagen alterations, mineral heterogeneity, and pore network disruption, consistent with a model in which compromised collagen integrity alters the mineral organization and the tubular network of dentin. Although requiring confirmation on larger cohorts, these findings provide a preliminary mechanistic framework for understanding how disruptions of the hierarchical structure of DI dentin, impairing its toughness, may originate from molecular collagen denaturation.
SN - 1742-7061
SN - 1878-7568
ER -