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Publisert 2018

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Tidsskrift : PLOS ONE , vol. 13 , p. 1–15 , 2018

Internasjonale standardnummer :
Trykt : 1932-6203
Elektronisk : 1932-6203

Publikasjonstype : Vitenskapelig artikkel

Bidragsytere : Rønning, Sissel; Pedersen, Mona Elisabeth; Berg, Ragnhild Stenberg; Kirkhus, Bente; Rødbotten, Rune

Sak : 4

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Kjetil Aune


Skeletal muscle function is highly dependent on the ability to regenerate, however, during
ageing or disease, the proliferative capacity is reduced, leading to loss of muscle function.
We have previously demonstrated the presence of vitamin K2 in bovine skeletal muscles,
but whether vitamin K has a role in muscle regulation and function is unknown. In this study,
we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to assess a
potential effect of vitamin K2 (MK-4) during myogenesis of muscle cells. Cell viability experiments
demonstrate that the amount of ATP produced by the cells was unchanged when
MK-4 was added, indicating viable cells. Cytotoxicity analysis show that MK-4 reduced the
lactate dehydrogenase (LDH) released into the media, suggesting that MK-4 was beneficial
to the muscle cells. Cell migration, proliferation and differentiation was characterised after
MK-4 incubation using wound scratch analysis, immunocytochemistry and real-time PCR
analysis. Adding MK-4 to the cells led to an increased muscle proliferation, increased gene
expression of the myogenic transcription factor myod as well as increased cell migration. In
addition, we observed a reduction in the fusion index and relative gene expression of muscle
differentiation markers, with fewer complex myotubes formed in MK-4 stimulated cells compared
to control cells, indicating that the MK-4 plays a significant role during the early
phases of muscle proliferation. Likewise, we see the same pattern for the relative gene
expression of collagen 1A, showing increased gene expression in proliferating cells, and
reduced expression in differentiating cells. Our results also suggest that MK-4 incubation
affect low density lipoprotein receptor-related protein 1 (LRP1) and the low-density lipoprotein
receptor (LDLR) with a peak in gene expression after 45 min of MK-4 incubation. Altogether,
our experiments show that MK-4 has a positive effect on muscle cell migration and
proliferation, which are two important steps during early myogenesis.