Osteopontin regulates type I collagen fibril formation in bone tissue.

Baptiste Depalle, Catriona M McGilvery, Sabah Nobakhti, Nouf Aldegaither, Sandra J Shefelbine, Alexandra E Porter

Acta biomaterialia 2021 Jan 15

filter terms:

Osteopontin (OPN) is a non-collagenous protein involved in biomineralization of bone tissue. Beyond its role in biomineralization, we show that osteopontin is essential to the quality of collagen fibrils in bone. Transmission electron microscopy revealed that, in Opn-/- tissue, the organization of the collagen fibrils was highly heterogeneous, more disorganized than WT bone and comprised of regions of both organized and disorganized matrix with a reduced density. The Opn-/- bone tissue also exhibited regions in which the collagen had lost its characteristic fibrillar structure, and the crystals were disorganized. Using nanobeam electron diffraction, we show that damage to structural integrity of collagen fibrils in Opn-/- bone tissue and their organization causes mineral disorganization, which could ultimately affect its mechanical integrity. STATEMENT OF SIGNIFICANCE: This study presents new evidence about the role of osteopontin (OPN) - a non-collagenous protein - on the structure and organization of the organic and mineral matrix in bone. In previous work, osteopontin has been suggested to regulate the nucleation and growth of bone mineral crystals and to form sacrificial bonds between mineralized collagen fibrils to enhance bone's toughness. Our findings show that OPN plays a crucial role before mineralization, during the formation of the collagen fibrils. OPN-deficient bones present a lower collagen content compared to wild type bone and, at the tissue level, collagen fibrils organization can be significantly altered in the absence of OPN. Our results suggest that OPN is critical for the formation and/or remodeling of bone collagen matrix. Our findings could lead to the development of new therapeutic strategies of bone diseases affecting collagen formation and remodeling. Copyright © 2020. Published by Elsevier Ltd.

Citation

Baptiste Depalle, Catriona M McGilvery, Sabah Nobakhti, Nouf Aldegaither, Sandra J Shefelbine, Alexandra E Porter. Osteopontin regulates type I collagen fibril formation in bone tissue. Acta biomaterialia. 2021 Jan 15;120:194-202