A Missense Variant in TP53 Could Be a Genetic Biomarker Associated with Bone Tissue Alterations-Reference-Cited by-同舟云学术

A Missense Variant in TP53 Could Be a Genetic Biomarker Associated with Bone Tissue Alterations

Published:2024-01-23 Issue:3 Volume:25 Page:1395
ISSN:1422-0067
Container-title:International Journal of Molecular Sciences
language:en
Short-container-title:IJMS

Author:

Usategui-Martín Ricardo¹²^ORCID,Galindo-Cabello Nadia¹²^ORCID,Pastor-Idoate Salvador²^ORCID,Fernández-Gómez José María¹,del Real Álvaro³^ORCID,Ferreño Diego⁴^ORCID,Lapresa Rebeca⁵⁶^ORCID,Martín-Rodriguez Francisco⁷,Riancho José A.³⁸,Almeida Ángeles⁵⁶^ORCID,Pérez-Castrillón José Luis⁷⁹

Affiliation:

1. Department of Cell Biology, Genetics, Histology and Pharmacology, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain

2. IOBA—Eye Institute, University of Valladolid, 47011 Valladolid, Spain

3. Department of Medicine and Psychiatry, Faculty of Medicine, Valdecilla Research Institute (IDIVAL), University of Cantabria, 39011 Santander, Spain

4. Laboratory of the Materials Science and Engineering Division—LADICIM, Faculty of Civil Engineering, University of Cantabria, 39011 Santander, Spain

5. Institute of Functional Biology and Genomics, University of Salamanca, CSIC, 37008 Salamanca, Spain

6. Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, University of Salamanca, CSIC, 37008 Salamanca, Spain

7. Department of Medicine, Dermatology and Toxicology, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain

8. Internal Medicine Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain

9. Internal Medicine Department, University Hospital Rio Hortega of Valladolid, 47012 Valladolid, Spain

Abstract

Metabolic bone diseases cover a broad spectrum of disorders that share alterations in bone metabolism that lead to a defective skeleton, which is associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, with TP53 being one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of TP53 is a genetic factor associated with several pathologies, including cancer, stroke, and osteoporosis. Here, we aim to analyze the influence of the TP53 Arg72Pro SNP on bone mass in humanized Tp53 Arg72Pro knock-in mice. This work reports on the influence of the TP53 Arg72Pro polymorphism in bone microarchitecture, OPG expression, and apoptosis bone status. The results show that the proline variant of the TP53 Arg72Pro polymorphism (Pro72-p53) is associated with deteriorated bone tissue, lower OPG/RANK ratio, and lower apoptosis in bone tissue. In conclusion, the TP53 Arg72Pro polymorphism modulates bone microarchitecture and may be a genetic biomarker that can be used to identify individuals with an increased risk of suffering metabolic bone alterations.

Funder

Ministerio de Ciencia e Innovación

Instituto de Salud Carlos III

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Link

https://www.mdpi.com/1422-0067/25/3/1395/pdf

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