What question did this study set out to answer?

This research aims to investigate the role of Factor VIII in bone and muscle development using FVIII knockout male mice.

March 13, 2026Open Access

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

Key Points

This research aims to investigate the role of Factor VIII in bone and muscle development using FVIII knockout male mice.
Studied musculoskeletal development in FVIII knockout male mice and wildtype controls.
Conducted proteomic analyses to compare bone metabolism-related proteins between groups.
Administered recombinant Factor VIII weekly to evaluate restoration effects on bone and muscle phenotypes.
Assessed muscle fiber type distribution and proteomic differences between FVIII knockout and wildtype mice.
FVIII knockout mice exhibited signs of osteoporosis, including altered bone structure and reduced vascularization.
Recombinant FVIII treatment successfully reversed several bone deficits in knockout mice.
Younger FVIII knockout mice showed unexpectedly larger muscle fibers and shifted muscle fiber type composition.
Proteomic and metabolomic analyses highlighted significant differences in bone and muscle profiles between FVIII knockout and wildtype mice.

Abstract

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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