Factor VIII restores bone parameters and modulates muscle proteo-metabolome in Factor VIII knockout male mice.

IF 20.1 1区医学 Q1 CELL & TISSUE ENGINEERING

Bone Research Pub Date : 2026-03-11 DOI:10.1038/s41413-025-00485-2

Antoine Babuty,Javier Muñoz-Garcia,Olivier D Christophe,Laurie Fradet,Manon Taupin,Denis Cochonneau,Emilie Ollivier,Frank Driessler,Claudia Lange,Oleksandr Boychenko,Marie-Françoise Heymann,Dominique Heymann

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引用次数: 0

Abstract

In addition to its role in hemostasis, Factor VIII (FVIII) has recently been shown to potentially impact angiogenesis, inflammation, osteopenia, and sarcopenia. This was explored here by studying the musculoskeletal development of FVIII knockout (FVIII-/-) male mice. These animals developed an osteoporotic phenotype with significant bone microarchitectural alteration, reduced vascularization, and a lower osteoblastic population. Proteomic analyses revealed differentiating bone metabolism-related proteins between FVIII-/- and wildtype mice. Weekly infusions of recombinant FVIII protein reversed this phenotype. Surprisingly, younger FVIII-/- mice had heavier muscles with larger fibers, shifted from type IIx to type IIb, not reversed by FVIII treatment. Significant proteomic and metabolomic differences between wildtype and FVIII-/- muscles were observed, some of which were reduced by FVIII treatment. This study provides the first comprehensive full-phenotypic characterization of bones and muscles in FVIII-/- mice and demonstrates the benefits of FVIII supplementation to normalize their musculoskeletal phenotype.

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在敲除因子VIII的雄性小鼠中，因子VIII恢复骨骼参数并调节肌肉蛋白质代谢组。

除了止血作用外，因子VIII （FVIII）最近被证明可能影响血管生成、炎症、骨质减少和肌肉减少。本文通过研究FVIII基因敲除（FVIII-/-）雄性小鼠的肌肉骨骼发育来探讨这一点。这些动物出现骨质疏松表型，伴有显著的骨微结构改变、血管化减少和成骨细胞数量减少。蛋白质组学分析显示FVIII-/-和野生型小鼠之间存在骨代谢相关蛋白的差异。每周输注重组FVIII蛋白可逆转这种表型。令人惊讶的是，年轻的FVIII-/-小鼠具有更重的肌肉和更大的纤维，从IIx型转变为IIb型，并没有被FVIII治疗逆转。在野生型和FVIII-/-肌肉之间观察到显著的蛋白质组学和代谢组学差异，其中一些在FVIII处理后减少。本研究首次提供了FVIII-/-小鼠骨骼和肌肉的全面全表型特征，并证明了补充FVIII对肌肉骨骼表型正常化的益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bone Research CELL & TISSUE ENGINEERING-

CiteScore

20.00

自引率

4.70%

发文量

289

审稿时长

20 weeks

期刊介绍： Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.