Role of nutritional factor menaquinone-7 in bone homeostasis and osteoporosis prevention

Yamaguchi, Masayoshi

doi:10.15761/imm.1000101

Cited by 8 publications

(4 citation statements)

References 79 publications

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“…Osteoblast DNA levels have been associated with OC expression, osteoprotegerin, NFκB ligand (RANKL), and RANK ligand promoter genes facilitated by vitamin K [74,75]. Furthermore, the vitamin K family participates in sphingolipids synthesis, in addition to their structural role, sphingolipids take part in proliferation, differentiation, and intercellular recognition activities of neurons [76]. Vitamin D3 cannot affect proliferation on its own, but does support osteoblast differentiation, as demonstrated by increased expression of typical markers such as runt-related transcription factor 2 (RUNX2), type I collagen, alkaline phosphatase, and OC [77,78,79].…”

Section: Discussionmentioning

confidence: 99%

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%

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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“…Researching the cis / trans isomers of MK-6 and MK-7 is very important from a biological point of view because only the trans forms of vitamins K 1 and K 2 manifest biological activity. The cis or cis / trans forms of menaquinones do not manifest such activity or manifest it at a very low level [ 5 , 9 , 28 , 36 ], this has been proven in the case of cis vitamin K 1 (Lowenthal and Rivera [ 25 ]) and mixtures of the cis / trans MK-6 isomers [ 37 ]. Based on these publications, it can be concluded that the cis or cis/trans isomers are chemical impurities of MK-7 and MK-6.…”

Section: Discussionmentioning

confidence: 99%

“…Vitamin K 1 is a cofactor of γ-glutamylcarboxylase that modifies hepatic blood coagulation factors. Vitamin K 2 has a higher affinity for extrahepatic γ-glutamylcarboxylase, modifying proteins such as osteocalcin, matrix Gla-protein or growth arrest specific gene 6 protein [ 7 , 8 , 9 ]. Vitamin K forms differ not only in target tissues but also in biological activity, as long-chain menaquinines show greater activity compared to short-chain ones due to the longer half-life in the blood [ 4 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Menaquinone-7 Content and Impurities in Oil and Non-Oil Dietary Supplements

et al. 2018

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Rapid, global technological development has caused the food industry to use concentrated food component sources like dietary supplements ever more commonly as part of the human diet. This study analysed the menaquinone-7 (MK-7) content of dietary supplements in oil capsule and hard tablet forms. A novel method for separating and measuring geometric isomers of MK-7 in dietary supplements was developed and validated. Eleven different isomers of cis/trans- menaquinone-7 were identified. Identification of cis/trans isomers was performed by combination of HPLC, UPLC and HRMS-QTOF detection, whereas their quantities were determined by DAD detection. The content of menaquinone impurities was ascertained, including cis/trans- menaquinone-6 isomers (5.5–16.9 µg per tablet/capsule) and cis/trans-menaquinone-7 isomers (70.9–218.7 µg tablet/capsule), which were most likely formed during the chemical synthesis of the menaquinone-7. The all-trans MK-7 content was lower than the isomeric form and often lower than what the labels declared. A new method of quantification, developed and validated for menaquinones in oil capsules, provided on average 90% recovery and a limit of quantification (LOQ) of approximately 1 µg mL−1.

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“…Cellular functions in osteoclastic and osteoblastic cells are performed by various proteins, whose expression is regulated by K2-7 ( Yamaguchi, 2014 ). Osteocalcin produced by osteoblasts binds to calcium present in blood circulation and leads it to the bone matrix.…”

Section: Vitamin K2-7 and Associated Diseasesmentioning

confidence: 99%

Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities

Jadhav¹,

Ajgaonkar²,

Saha³

et al. 2022

Front. Pharmacol.

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Vitamin K2-7, also known as menaquinone-7 (MK-7) is a form of vitamin K that has health-beneficial effects in osteoporosis, cardiovascular disease, inflammation, cancer, Alzheimer’s disease, diabetes and peripheral neuropathy. Compared to vitamin K1 (phylloquinone), K2-7 is absorbed more readily and is more bioavailable. Clinical studies have unequivocally demonstrated the utility of vitamin K2-7 supplementation in ameliorating peripheral neuropathy, reducing bone fracture risk and improving cardiovascular health. We examine how undercarboxylated osteocalcin (ucOC) and matrix Gla protein (ucMGP) are converted to carboxylated forms (cOC and cMGP respectively) by K2-7 acting as a cofactor, thus facilitating the deposition of calcium in bones and preventing vascular calcification. K2-7 is beneficial in managing bone loss because it upregulates osteoprotegerin which is a decoy receptor for RANK ligand (RANKL) thus inhibiting bone resorption. We also review the evidence for the health-beneficial outcomes of K2-7 in diabetes, peripheral neuropathy and Alzheimer’s disease. In addition, we discuss the K2-7-mediated suppression of growth in cancer cells via cell-cycle arrest, autophagy and apoptosis. The mechanistic basis for the disease-modulating effects of K2-7 is mediated through various signal transduction pathways such as PI3K/AKT, MAP Kinase, JAK/STAT, NF-κB, etc. Interestingly, K2-7 is also responsible for suppression of proinflammatory mediators such as IL-1α, IL-1β and TNF-α. We elucidate various genes modulated by K2-7 as well as the clinical pharmacometrics of vitamin K2-7 including K2-7-mediated pharmacokinetics/pharmacodynamics (PK/PD). Further, we discuss the current status of clinical trials on K2-7 that shed light on dosing strategies for maximum health benefits. Taken together, this is a synthetic review that delineates the health-beneficial effects of K2-7 in a clinical setting, highlights the molecular basis for these effects, elucidates the clinical pharmacokinetics of K2-7, and underscores the need for K2-7 supplementation in the global diet.

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Role of nutritional factor menaquinone-7 in bone homeostasis and osteoporosis prevention

Cited by 8 publications

References 79 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

Analysis of Menaquinone-7 Content and Impurities in Oil and Non-Oil Dietary Supplements

Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities

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