Recent advances in vitamin K-dependent Gla-containing proteins and vitamin K nutrition

Shiraki, Masataka; Tsugawa, Naoko; Okano, Toshio

doi:10.1016/j.afos.2015.07.009

Cited by 21 publications

(13 citation statements)

References 162 publications

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“…The K vitamin family supports biosynthesis of OC by participating in post-translational carboxylation of Gla residues of OC propeptides [26]. In contrast, carboxylated OC binds calcium to bone hydroxyapatite, thus supporting bone metabolism [81].…”

Section: Discussionmentioning

confidence: 99%

“…This could be because post-translational modification of OC depends on both vitamin D3 and vitamin K [37]. Vitamin D3 activates γ-glutamylcarboxylase for which vitamin K is a cofactor [26,84]. Moreover, vitamin K intensifies the synthesis and accumulation of carboxylated OC [82], thereby supporting hydroxyapatite deposition on collagen fibers.…”

Section: Discussionmentioning

confidence: 99%

“…Vitamin D promotes vitamin K-dependent protein production while vitamin K activates proteins involved in bone metabolism. Vitamin K acts as a cofactor in the carboxylation of glutamic acid (Glu) to Gla and the metabolically active form of OC, which can bind and deposit calcium in the extracellular matrix [11,26]. In vitro, vitamin K2 was shown to promote osteoclast apoptosis in a dose-dependent manner and to suppress osteoblast apoptosis [27,28].…”

Section: Introductionmentioning

confidence: 99%

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Beneficial Effects of Vitamins K and D3 on Redox Balance of Human Osteoblasts Cultured with Hydroxyapatite-Based Biomaterials

Ambrożewicz

Muszyńska

Tokajuk

et al. 2019

Cells

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Hydroxyapatite-based biomaterials are commonly used in surgery to repair bone damage. However, the introduction of biomaterials into the body can cause metabolic alterations, including redox imbalance. Because vitamins D3 and K (K1, MK-4, MK-7) have pronounced osteoinductive, anti-inflammatory, and antioxidant properties, it is suggested that they may reduce the adverse effects of biomaterials. The aim of this study was to investigate the effects of vitamins D3 and K, used alone and in combination, on the redox metabolism of human osteoblasts (hFOB 1.19 cell line) cultured in the presence of hydroxyapatite-based biomaterials (Maxgraft, Cerabone, Apatos, and Gen-Os). Culturing of the osteoblasts in the presence of hydroxyapatite-based biomaterials resulted in oxidative stress manifested by increased production of reactive oxygen species and decrease of glutathione level and glutathione peroxidase activity. Such redox imbalance leads to lipid peroxidation manifested by an increase of 4-hydroxynonenal level, which is known to influence the growth of bone cells. Vitamins D3 and K were shown to help maintain redox balance and prevent lipid peroxidation in osteoblasts cultured with hydroxyapatite-based biomaterials. The strongest effect was observed for the combination of vitamin D3 and MK-7. Moreover, vitamins promoted growth of the osteoblasts, manifested by increased DNA biosynthesis. Therefore, it is suggested that the use of vitamins D3 and K may protect redox balance and support the growth of osteoblasts affected by hydroxyapatite-based biomaterials.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Beneficial Effects of Vitamins K and D3 on Redox Balance of Human Osteoblasts Cultured with Hydroxyapatite-Based Biomaterials

Ambrożewicz

Muszyńska

Tokajuk

et al. 2019

Cells

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“…Gas6, the latest addition to the family of VK‐dependent proteins, is reported to have important roles in the regulation of insulin sensitivity, glucose homeostasis, inflammation, adiposity, and other metabolic disorders . The enzyme GGCX catalyzes the posttranslational formation of gamma‐glutamyl–carboxylated Gas6 (cGas6) by using VK as a cofactor . Some studies reported that higher Gas6 levels (or Gas6 polymorphism) are associated with lower plasma glucose, glycated hemoglobin, and IR among T2D and obese subjects .…”

Section: Discussionmentioning

confidence: 99%

“…1 The enzyme GGCX catalyzes the posttranslational formation of gammaglutamyl-carboxylated Gas6 (cGas6) by using VK as a cofactor. 22 Some studies reported that higher Gas6 levels (or Gas6 polymorphism) are associated with lower plasma glucose, glycated hemoglobin, and IR among T2D and obese subjects. 2,4,23 However, another study reported a strong positive cor-relation of Gas6 with IR and inflammation among obese subjects.…”

Section: Discussionmentioning

confidence: 99%

Gamma‐glutamyl–carboxylated Gas6 mediates positive role of vitamin K on lowering hyperglycemia in type 2 diabetes

Dihingia

Ozah

Borah

et al. 2019

Annals of the New York Academy of Sciences

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The role of gamma‐glutamyl–carboxylated growth arrest–specific 6 (cGas6) in mediating the beneficial effect of vitamin K (VK) on regulating glucose metabolism remains elusive. We took a three‐pronged approach—evaluating human type 2 diabetes (T2D), high‐fat diet (HFD)–fed mice, and in vitro cultured myotubes—to address this. Blood samples were collected from both T2D patients and control subjects; skeletal muscle and blood samples were collected from HFD–fed mice with or without VK supplementation (1, 3, and 5 µg/kg BW, 8 weeks); and the molecular mechanism of cGas6 was dissected using GGCX, Gas6, AXL, or IR siRNA–transfected cultured myotubes. Plasma cGas6 and VK were significantly lower in T2D patients compared with control; and cGas6 and the cGas6/Gas6 ratio were positively correlated with VK and inversely correlated with fasting glucose in T2D patients, suggesting an important role for plasma VK and cGas6 in maintaining glucose homeostasis in T2D. Animal studies revealed that VK supplementation dose‐dependently upregulated plasma cGas6; stimulated the protein expression of cGas6, PI3K, pAKT, and GLUT4 in skeletal muscle; and reduced hyperglycemia in HFD‐fed T2D mice. And in vitro mRNA knockdown studies demonstrated the requirement of cGas6 in mediating the positive effect of VK on glucose metabolism via stimulating the PI3K/pAKT/GLUT4 signaling pathway in high glucose–treated myotubes. These results demonstrate a significant involvement of cGas6 in mediating the beneficial effect of VK on regulating glucose homeostasis in T2D.

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Comparison of concurrent treatment with vitamin K2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis: Japanese Osteoporosis Intervention Trial-03

Tanaka

Miyazaki²,

Uemura

et al. 2016

J Bone Miner Metab

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The aim of this study was to investigate the efficacy of concurrent treatment with vitamin K and risedronate compared with treatment with risedronate alone in patients with osteoporosis and to explore subsets of patients for which concurrent treatment is particularly efficacious. Women with osteoporosis aged 65 years or older were recruited from 123 institutes in Japan and allocated to take either vitamin K (45 mg/day) and risedronate (2.5 mg/day or 17.5 mg/week) or risedronate (2.5 mg/day or 17.5 mg/week) alone. The primary end point was the incidence of any fracture (vertebral and nonvertebral). The secondary end points were bone mineral density, height, undercarboxylated osteocalcin concentration, quality of life, and safety. Over a 2-year follow-up, vertebral or nonvertebral fractures occurred in 117 or 22 sites respectively among 931 patients in the risedronate and vitamin K group and in 104 or 26 sites respectively among 943 patients in the risedronate alone group. The rates of any incident fracture were similar between the two groups (incidence rate ratio 1.074, 95 % confidence interval 0.811-1.422, p = 0.62), implying that the primary end point was not met. There were no differences in the degree of increase in bone mineral density between the two groups. Undercarboxylated osteocalcin concentration decreased from 5.81 ± 3.93 ng/mL to 2.59 ± 1.52 ng/mL at 6 months in the risedronate and vitamin K group, whereas the change in the risedronate alone group was minimal (from 5.96 ± 4.36 ng/mL to 4.05 ± 3.40 ng/mL at 6 months) (p < 0.01). The treatment discontinuation rate was higher in the risedronate and vitamin K group than in the risedronate alone group (10.0 % vs 6.7 %). No unknown adverse drug reactions were reported. In conclusion, concurrent treatment with vitamin K and risedronate was not efficacious compared with monotherapy with risedronate in terms of fracture prevention.

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Recent advances in vitamin K-dependent Gla-containing proteins and vitamin K nutrition

Cited by 21 publications

References 162 publications

Beneficial Effects of Vitamins K and D3 on Redox Balance of Human Osteoblasts Cultured with Hydroxyapatite-Based Biomaterials

Beneficial Effects of Vitamins K and D3 on Redox Balance of Human Osteoblasts Cultured with Hydroxyapatite-Based Biomaterials

Gamma‐glutamyl–carboxylated Gas6 mediates positive role of vitamin K on lowering hyperglycemia in type 2 diabetes

Comparison of concurrent treatment with vitamin K2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis: Japanese Osteoporosis Intervention Trial-03

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