Vitamin K Nutrition and Bone Health

Tsugawa, Naoko; Shiraki, Masataka

doi:10.3390/nu12071909

Cited by 57 publications

(45 citation statements)

References 79 publications

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“…This study provides a framework for future studies, both in vitro and in vivo for the role of MK-7 in bone formation and fracture healing. This corroborates observations, from longitudinal and interventional trials on increased bone mineral density following either vitamin K2 supplementation (Sato et al, 2020 ) or an increased amount of vitamin K2 in the diet (Tsugawa and Shiraki, 2020 ). Furthermore, the role of VKDPs in iPSC derived products has not been widely explored.…”

Section: Discussionsupporting

confidence: 89%

“…Moreover, we interrogated the differentiation trajectory, given basic and clinical science reports on pro-osteogenic properties of MK-7, such as promoting bone formation, bone density and strength, as well as inhibiting bone loss (Sato et al, 2020 ). Furthermore, vitamin K deficiency is associated with increased fracture rate and decreased bone mass density in a variety of patient cohorts (Tsugawa and Shiraki, 2020 ). Therefore, we determined whether MK-7 supplementation may further propagate an osteogenic phenotype of iMSCs.…”

Section: Discussionmentioning

confidence: 99%

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Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells

Akbulut

Wasilewski

Rapp

et al. 2021

Front. Cell Dev. Biol.

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Development of clinical stem cell interventions are hampered by immature cell progeny under current protocols. Human mesenchymal stem cells (hMSCs) are characterized by their ability to self-renew and differentiate into multiple lineages. Generating hMSCs from pluripotent stem cells (iPSCs) is an attractive avenue for cost-efficient and scalable production of cellular material. In this study we generate mature osteoblasts from iPSCs using a stable expandable MSC intermediate, refining established protocols. We investigated the timeframe and phenotype of cells under osteogenic conditions as well as the effect of menaquinone-7 (MK-7) on differentiation. From day 2 we noted a significant increase in RUNX2 expression under osteogenic conditions with MK-7, as well as decreases in ROS species production, increased cellular migration and changes to dynamics of collagen deposition when compared to differentiated cells that were not treated with MK-7. At day 21 OsteoMK-7 increased alkaline phosphatase activity and collagen deposition, as well as downregulated RUNX2 expression, suggesting to a mature cellular phenotype. Throughout we note no changes to expression of osteocalcin suggesting a non-canonical function of MK-7 in osteoblast differentiation. Together our data provide further mechanistic insight between basic and clinical studies on extrahepatic activity of MK-7. Our findings show that MK-7 promotes osteoblast maturation thereby increasing osteogenic differentiation.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells

Akbulut

Wasilewski

Rapp

et al. 2021

Front. Cell Dev. Biol.

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“…Bone strength is determined by bone mineral content (BMC) and its quality and is associated with biological senescence and vitamin (B, D, K) deficiencies. As VK activates tissue-specific VKDPs, such as prothrombin, OC, or MGP, via the γ-carboxylation of Glu to Gla molecules, insufficient VKDPs γ-carboxylation is a sensitive, tissue-specific marker of VK deficiency [40]. Several studies revealed that VK is involved in bone metabolism and inhibits bone resorption in a dose-dependent manner.…”

Section: Vitamin K In Bone Healthmentioning

confidence: 99%

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

2021

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As human life expectancy is rising, the incidence of age-associated diseases will also increase. Scientific evidence has revealed that healthy diets, including good fats, vitamins, minerals, or polyphenolics, could have antioxidant and anti-inflammatory activities, with antiaging effects. Recent studies demonstrated that vitamin K is a vital cofactor in activating several proteins, which act against age-related syndromes. Thus, vitamin K can carboxylate osteocalcin (a protein capable of transporting and fixing calcium in bone), activate matrix Gla protein (an inhibitor of vascular calcification and cardiovascular events) and carboxylate Gas6 protein (involved in brain physiology and a cognitive decline and neurodegenerative disease inhibitor). By improving insulin sensitivity, vitamin K lowers diabetes risk. It also exerts antiproliferative, proapoptotic, autophagic effects and has been associated with a reduced risk of cancer. Recent research shows that protein S, another vitamin K-dependent protein, can prevent the cytokine storm observed in COVID-19 cases. The reduced activation of protein S due to the pneumonia-induced vitamin K depletion was correlated with higher thrombogenicity and possibly fatal outcomes in COVID-19 patients. Our review aimed to present the latest scientific evidence about vitamin K and its role in preventing age-associated diseases and/or improving the effectiveness of medical treatments in mature adults ˃50 years old.

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“…Third, vitamin K status, which is known to affect OC carboxylation, has not been evaluated in the present series due to unavailability of accurate tools such as high-performance liquid chromatography–tandem mass spectrometry for the assessment of vitamin K homologues, phylloquinone (vitamin K1) and menaquinones (MK-4 and MK-7). However, it is of note that measuring uncarboxylated vitamin K-dependent protein (i.e., osteocalcin) levels is considered the most accurate and convenient method for assessing tissue-specific vitamin K deficiency or insufficiency ( 56 ). Indeed, here failure in detecting association between plasma uOC levels and most of the parameters related with body composition, may suggest that vitamin K replenishment is not a major determinant of the potential relationship with muscle mass and function.…”

Section: Discussionmentioning

confidence: 99%

Circulating Carboxylated Osteocalcin Correlates With Skeletal Muscle Mass and Risk of Fall in Postmenopausal Osteoporotic Women

et al. 2021

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BackgroundBone and skeletal muscle represent a single functional unit. We cross-sectionally investigated body composition, risk of fall and circulating osteocalcin (OC) isoforms in osteoporotic postmenopausal women to test the hypothesis of an involvement of OC in the bone-muscle crosstalk.Materials and MethodsTwenty-nine non-diabetic, non-obese, postmenopausal osteoporotic women (age 72.4 ± 6.8 years; BMI 23.0 ± 3.3 kg/m2) underwent to: 1) fasting blood sampling for biochemical and hormone assays, including carboxylated (cOC) and uncarboxylated (uOC) osteocalcin; 2) whole-body dual energy X-ray absorptiometry (DXA) to assess total and regional body composition; 3) magnetic resonance imaging to determine cross-sectional muscle area (CSA) and intermuscular adipose tissue (IMAT) of thigh muscles; 4) risk of fall assessment through the OAK system.ResultsAppendicular skeletal muscle index (ASMMI) was low in 45% of patients. Forty percent got a low OAK score, consistent with moderate-severe risk of fall, which was predicted by low legs lean mass and increased total fat mass. Circulating cOC levels showed significantly correlated with βCTx-I, lean mass parameters including IMAT, and OAK score. Fractured and unfractured women did not differ for any of the analyzed parameters, though cOC and uOC positively correlated with legs lean mass, OAK score and bone markers only in fractured women.ConclusionsData supported the relationship between OC and skeletal muscle mass and function in postmenopausal osteoporotic women. Serum cOC, but not uOC, emerges as mediator in the bone-muscle crosstalk. Circulating cOC and uOC levels may be differentially regulated in fractured and unfractured osteoporotic women, suggesting underlying differences in bone metabolism.

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Vitamin K Nutrition and Bone Health

Cited by 57 publications

References 79 publications

Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells

Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

Circulating Carboxylated Osteocalcin Correlates With Skeletal Muscle Mass and Risk of Fall in Postmenopausal Osteoporotic Women

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