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Roles of vitamin K‑dependent protein in biomineralization (Review)

  • Authors:
    • Meng Zhang
    • Qingqi Zhang
    • Pengfei Du
    • Xin Chen
    • Yumei Zhang
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    Affiliations: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 6
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    Published online on: November 24, 2023
       https://doi.org/10.3892/ijmm.2023.5330
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Abstract

Vitamin K (VK), a fat‑soluble vitamin, is well known as an anticoagulant in the clinic. It is essential for the post‑translational activation of VK‑dependent proteins (VKDPs) because hydroquinone VK is a cofactor of glutamine carboxylase. At present, 17 VKDPs are known, which are mainly involved in coagulation and calcification. When Glu residues are carboxylated to Gla residues, these proteins gain a higher calcium‑binding ability, which explains why VK has an important role in blood coagulation and biomineralization. However, the current view on the role of VK and several VKDPs in biomineralization remains inconsistent. For instance, conflicting results have been reported regarding the effect of osteocalcin gene knockout on the bone of mice; matrix Gla protein (MGP) promotes osteoblasts mineralization but inhibits vascular smooth muscle cell mineralization. The present review aimed to summarize the existing evidence that several VKDPs, including osteocalcin, MGP, Gla‑rich protein and growth arrest specific 6 are closely related to calcification, including bone health, vascular calcification and lithiasis. The current review discussed these controversies and provided suggestions for future studies on VKDPs, i.e. taking into account dietary habits, geographical environments and genetic backgrounds.
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1 

Guibert C and Landoulsi J: Enzymatic approach in calcium phosphate biomineralization: A contribution to reconcile the physicochemical with the physiological view. Int J Mol Sci. 22:129572021.

2 

Arnold A, Dennison E, Kovacs CS, Mannstadt M, Rizzoli R, Brandi ML, Clarke B and Thakker RV: Hormonal regulation of biomineralization. Nat Rev Endocrinol. 17:261–275. 2021.

3 

Tang S, Dong Z, Ke X, Luo J and Li J: Advances in biomineralization-inspired materials for hard tissue repair. Int J Oral Sci. 13:422021.

4 

Villa-Bellosta R: Vascular calcification: Key roles of phosphate and pyrophosphate. Int J Mol Sci. 22:135362021.

5 

Ziemińska M, Sieklucka B and Pawlak K: Vitamin K and D supplementation and bone health in chronic kidney disease-apart or together? Nutrients. 13:8092021.

6 

Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P, Munns CF, Lazaretti-Castro M, Giustina A and Bilezikian J: Skeletal and extraskeletal actions of vitamin D: Current evidence and outstanding questions. Endocr Rev. 40:1109–1151. 2019.

7 

Brzezińska O, Łukasik Z, Makowska J and Walczak K: Role of vitamin C in osteoporosis development and treatment-a literature review. Nutrients. 12:23942020.

8 

Jin C, Tan K, Yao Z, Lin BH, Zhang DP, Chen WK, Mao SM, Zhang W, Chen L, Lin Z, et al: A novel anti-osteoporosis mechanism of VK2: Interfering with ferroptosis via AMPK/SIRT1 pathway in type 2 diabetic osteoporosis. J Agric Food Chem. 71:2745–2761. 2023.

9 

Wang H, Li L, Zhang N and Ma Y: Vitamin K2 improves osteogenic differentiation by inhibiting STAT1 via the Bcl-6 and IL-6/JAK in C3H10 T1/2 clone 8 cells. Nutrients. 14:29342022.

10 

Akbulut AC, Wasilewski GB, Rapp N, Forin F, Singer H, Czogalla-Nitsche KJ and Schurgers LJ: Menaquinone-7 supplementation improves osteogenesis in pluripotent stem cell derived mesenchymal stem cells. Front Cell Dev Biol. 8:6187602021.

11 

Stock M and Schett G: Vitamin K-dependent proteins in skeletal development and disease. Int J Mol Sci. 22:93282021.

12 

Mladěnka P, Macáková K, Kujovská Krčmová L, Javorská L, Mrštná K, Carazo A, Protti M, Remião F and Nováková L; OEMONOM researchers and collaborators: Vitamin K-sources, physiological role, kinetics, deficiency, detection, therapeutic use, and toxicity. Nutr Rev. 80:677–698. 2022.

13 

National Research Council: Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. National Academy Press; Washington, DC, USA: pp. 162–196. 2000

14 

World Health Organization and Food and Agriculture Organization of the United Nations: Vitamin K. Vitamin and mineral requirements in human nutrition. 2nd. World Health Organization; Geneva, Switzerland: pp. 108–129. 2004

15 

Takada T, Yamanashi Y, Konishi K, Yamamoto T, Toyoda Y, Masuo Y, Yamamoto H and Suzuki H: NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy. Sci Transl Med. 7:275ra232015.

16 

Matsuo M, Ogata Y, Yamanashi Y and Takada T: ABCG5 and ABCG8 Are involved in vitamin K transport. Nutrients. 15:9982023.

17 

Lai Y, Masatoshi H, Ma Y, Guo Y and Zhang B: Role of vitamin K in intestinal health. Front Immunol. 12:7915652022.

18 

Welsh J, Bak MJ and Narvaez CJ: New insights into vitamin K biology with relevance to cancer. Trends Mol Med. 28:864–881. 2022.

19 

Sultana H, Komai M and Shirakawa H: The role of vitamin K in cholestatic liver disease. Nutrients. 13:25152021.

20 

Kaesler N, Schurgers LJ and Floege J: Vitamin K and cardiovascular complications in chronic kidney disease patients. Kidney Int. 100:1023–1036. 2021.

21 

Regulska-Ilow B, Różańska D, Zatońska K and Szuba A: Estimation of vitamin K content and its sources in the diet of the polish participants of the PURE study. Nutrients. 14:19172022.

22 

Mishima E, Ito J, Wu Z, Nakamura T, Wahida A, Doll S, Tonnus W, Nepachalovich P, Eggenhofer E, Aldrovandi M, et al: A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature. 608:778–783. 2022.

23 

Shearer MJ and Okano T: Key pathways and regulators of vitamin K function and intermediary metabolism. Annu Rev Nutr. 38:127–151. 2018.

24 

Dahms SO, Demir F, Huesgen PF, Thorn K and Brandstetter H: Sirtilins-the new old members of the vitamin K-dependent coagulation factor family. J Thromb Haemost. 17:470–481. 2019.

25 

Fusaro M, Tripepi G, Plebani M, Politi C, Aghi A, Taddei F, Schileo E, Zaninotto M, La Manna G, Cianciolo G, et al: The vessels-bone axis: Iliac artery calcifications, vertebral fractures and vitamin K from VIKI study. Nutrients. 13:35672021.

26 

Nalevaiko JZ, Marques JVO, Oliveira MF, Raetsch AWP, Marques GL, Petterle RR, Moreira CA and Borba VZC: Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin. Bone. 150:1160002021.

27 

Poterucha TJ and Goldhaber SZ: Warfarin and vascular calcification. Am J Med. 129:635.e1–e4. 2016.

28 

Tantisattamo E, Han KH and O'Neill WC: Increased vascular calcification in patients receiving warfarin. Arterioscler Thromb Vasc Biol. 35:237–242. 2015.

29 

Verma D, Kumar R, Pereira RS, Karantanou C, Zanetti C, Minciacchi VR, Fulzele K, Kunz K, Hoelper S, Zia-Chahabi S, et al: Vitamin K antagonism impairs the bone marrow microenvironment and hematopoiesis. Blood. 134:227–238. 2019.

30 

Vimalraj S: Alkaline phosphatase: Structure, expression and its function in bone mineralization. Gene. 754:1448552020.

31 

Murshed M: Mechanism of bone mineralization. Cold Spring Harb Perspect Med. 8:a0312292018.

32 

Ma ML, Ma ZJ, He YL, Sun H, Yang B, Ruan BJ, Zhan WD, Li SX, Dong H and Wang YX: Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials. Front Public Health. 10:9796492022.

33 

Jadhav N, Ajgaonkar S, Saha P, Gurav P, Pandey A, Basudkar V, Gada Y, Panda S, Jadhav S, Mehta D and Nair S: Molecular pathways and roles for vitamin K2-7 as a health-beneficial nutraceutical: Challenges and opportunities. Front Pharmacol. 13:8969202022.

34 

Salma, Ahmad SS, Karim S, Ibrahim IM, Alkreathy HM, Alsieni M and Khan MA: Effect of vitamin K on bone mineral density and fracture risk in adults: Systematic review and meta-analysis. Biomedicines. 10:10482022.

35 

Knapen MHJ, Drummen NE, Smit E, Vermeer C and Theuwissen E: Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 24:2499–2507. 2013.

36 

Li X, Yang HY and Giachelli CM: BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells. Atherosclerosis. 199:271–277. 2008.

37 

Ciccarelli G, Conte S, Cimmino G, Maiorano P, Morrione A and Giordano A: Mitochondrial dysfunction: The hidden player in the pathogenesis of atherosclerosis? Int J Mol Sci. 24:10862023.

38 

Rao Z, Zheng Y, Xu L, Wang Z, Zhou Y, Chen M, Dong N, Cai Z and Li F: Endoplasmic reticulum stress and pathogenesis of vascular calcification. Front Cardiovasc Med. 9:9180562022.

39 

Siltari A and Vapaatalo H: Vascular calcification, vitamin K and warfarin therapy-possible or plausible connection? Basic Clin Pharmacol Toxicol. 122:19–24. 2018.

40 

Kosciuszek ND, Kalta D, Singh M and Savinova OV: Vitamin K antagonists and cardiovascular calcification: A systematic review and meta-analysis. Front Cardiovasc Med. 9:9385672022.

41 

Levy DS, Grewal R and Le TH: Vitamin K deficiency: an emerging player in the pathogenesis of vascular calcification and an iatrogenic consequence of therapies in advanced renal disease. Am J Physiol Renal Physiol. 319:F618–F623. 2020.

42 

Shioi A, Morioka T, Shoji T and Emoto M: The inhibitory roles of vitamin K in progression of vascular calcification. Nutrients. 12:5832020.

43 

Li Y, Lu X, Yang B, Mao J, Jiang S, Yu D, Pan J, Cai T, Yasui T and Gao B: Vitamin K1 inhibition of renal crystal formation through matrix Gla protein in the kidney. Kidney Blood Press Res. 44:1392–1403. 2019.

44 

Hu B, Wang T, Liu Z, Guo X, Yang J, Liu J, Wang S and Ye Z: Decreased expression of vitamin K epoxide reductase complex subunit 1 in kidney of patients with calcium oxalate urolithiasis. J Huazhong Univ Sci Technolog Med Sci. 31:807–814. 2011.

45 

Hewett-Emmett D: Amino acid sequence homology and the vitamin K-dependent proteins. Bibl Haematol. 44:94–104. 1977.

46 

Barille S, Pellat-Deceunynck C, Bataille R and Amiot M: Ectopic secretion of osteocalcin, the major non-collagenous bone protein, by the myeloma cell line NCI-H929. J Bone Miner Res. 11:466–471. 1996.

47 

Cancela ML, Laizé V and Conceição N: Matrix Gla protein and osteocalcin: From gene duplication to neofunctionalization. Arch Biochem Biophys. 561:56–63. 2014.

48 

Hauschka PV, Lian JB, Cole DE and Gundberg CM: Osteocalcin and matrix Gla protein: Vitamin K-dependent proteins in bone. Physiol Rev. 69:990–1047. 1989.

49 

Xu Y, Shen L, Liu L, Zhang Z and Hu W: Undercarboxylated osteocalcin and its associations with bone mineral density, bone turnover markers, and prevalence of osteopenia and osteoporosis in chinese population: A cross-sectional study. Front Endocrinol (Lausanne). 13:8439122022.

50 

Li R, Zhu X, Zhang M, Zong G and Zhang K: Association of serum periostin level with classical bone turnover markers and bone mineral density in Shanghai Chinese postmenopausal women with osteoporosis. Int J Gen Med. 14:7639–7646. 2021.

51 

Lateef M, Baig M and Azhar A: Estimation of serum osteocalcin and telopeptide-C in postmenopausal osteoporotic females. Osteoporos Int. 21:751–755. 2010.

52 

Bailey S, Poundarik AA, Sroga GE and Vashishth D: Structural role of osteocalcin and its modification in bone fracture. Appl Phys Rev. 10:0114102023.

53 

Kavukcuoglu NB, Patterson-Buckendahl P and Mann AB: Effect of osteocalcin deficiency on the nanomechanics and chemistry of mouse bones. J Mech Behav Biomed Mater. 2:348–354. 2009.

54 

Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, et al: Increased bone formation in osteocalcin-deficient mice. Nature. 382:448–452. 1996.

55 

Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, et al: Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 12:1260–1268. 1988.

56 

Berezovska O, Yildirim G, Budell WC, Yagerman S, Pidhaynyy B, Bastien C, van der Meulen MCH and Dowd TL: Osteocalcin affects bone mineral and mechanical properties in female mice. Bone. 128:1150312019.

57 

Hosseini S, Naderi-Manesh H, Vali H, Baghaban Eslaminejad M, Azam Sayahpour F, Sheibani S and Faghihi S: Contribution of osteocalcin-mimetic peptide enhances osteogenic activity and extracellular matrix mineralization of human osteoblast-like cells. Colloids Surf B Biointerfaces. 173:662–671. 2019.

58 

Tsao YT, Huang YJ, Wu HH, Liu YA, Liu YS and Lee OK: Osteocalcin Mediates biomineralization during osteogenic maturation in human mesenchymal stromal cells. Int J Mol Sci. 18:1592017.

59 

Gössl M, Mödder UI, Atkinson EJ, Lerman A and Khosla S: Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis. J Am Coll Cardiol. 52:1314–1325. 2008.

60 

Flammer AJ, Gössl M, Widmer RJ, Reriani M, Lennon R, Loeffler D, Shonyo S, Simari RD, Lerman LO, Khosla S and Lerman A: Osteocalcin positive CD133+/CD34-/KDR+ progenitor cells as an independent marker for unstable atherosclerosis. Eur Heart J. 33:2963–2939. 2012.

61 

Pal SN, Rush C, Parr A, Van Campenhout A and Golledge J: Osteocalcin positive mononuclear cells are associated with the severity of aortic calcification. Atherosclerosis. 210:88–93. 2010.

62 

Shen Y, Chen L, Zhou J, Wang C, Gao F, Zhu W, Hu G, Ma X, Xia H and Bao Y: Low total osteocalcin levels are associated with all-cause and cardiovascular mortality among patients with type 2 diabetes: A real-world study. Cardiovasc Diabetol. 21:982022.

63 

Shahrour HE, Al Fahom S, Al-Massarani G, AlSaadi AR and Magni P: Osteocalcin-expressing endothelial progenitor cells and serum osteocalcin forms are independent biomarkers of coronary atherosclerotic disease severit in male and female patients. J Endocrinol Invest. 45:1173–1180. 2022.

64 

Guo X, Li Y, Zhou Y, Zhang C, Liang S, Zheng Y, Chen X and Cai G: Osteocalcin association with vascular function in chronic kidney disease. J Clin Hypertens (Greenwich). 24:928–936. 2022.

65 

Chai S, Chen Y, Xin S, Yuan N, Liu Y, Sun J, Meng X and Qi Y: Positive association of leptin and artery calcification of lower extremity in patients with type 2 diabetes mellitus: A pilot study. Front Endocrinol (Lausanne). 12:5835752021.

66 

Millar SA, John SG, McIntyre CW, Ralevic V, Anderson SI and O'Sullivan SE: An investigation into the role of osteocalcin in human arterial smooth muscle cell calcification. Front Endocrinol (Lausanne). 11:3692020.

67 

Keryakos HKH, Okaily NI, Boulis MAY and Salama AMS: Osteocalcin and vascular calcification in hemodialysis patients: An observational cohort study. Int Urol Nephrol. 53:1015–1023. 2021.

68 

Hwang YC, Kang M, Cho IJ, Jeong IK, Ahn KJ, Chung HY and Lee MK: Association between the circulating total osteocalcin level and the development of cardiovascular disease in middle-aged men: A mean 8.7-year longitudinal follow-up study. J Atheroscler Thromb. 22:136–143. 2015.

69 

Millar SA, Anderson SI and O'sullivan SE: Human vascular cell responses to the circulating bone hormone osteocalcin. J Cell Physiol. 234:21039–21048. 2019.

70 

Huang L, Yang L, Luo L, Wu P and Yan S: Osteocalcin improves metabolic profiles, body composition and arterial stiffening in an induced diabetic rat model. Exp Clin Endocrinol Diabetes. 125:234–240. 2017.

71 

Dou J, Li H, Ma X, Zhang M, Fang Q, Nie M, Bao Y and Jia W: Osteocalcin attenuates high fat diet-induced impairment of endothelium-dependent relaxation through Akt/eNOS-dependent pathway. Cardiovasc Diabetol. 13:742014.

72 

Price PA and Williamson MK: Primary structure of bovine matrix Gla protein, a new vitamin K-dependent bone protein. J Biol Chem. 260:14971–14975. 1985.

73 

Cancela L, Hsieh CL, Francke U and Price PA: Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene. J Biol Chem. 265:15040–15048. 1990.

74 

Price PA, Rice JS and Williamson MK: Conserved phosphorylation of serines in the Ser-X-Glu/Ser(P) sequences of the vitamin K-dependent matrix Gla protein from shark, lamb, rat, cow, and human. Protein Sci. 3:822–830. 1994.

75 

Boer CG, Szilagyi I, Nguyen NL, Neogi T, Meulenbelt I, Ikram MA, Uitterlinden AG, Bierma-Zeinstra S, Stricker BH and van Meurs JB: Vitamin K antagonist anticoagulant usage is associated with increased incidence and progression of osteoarthritis. Ann Rheum Dis. 80:598–604. 2021.

76 

Houtman E, Coutinho de Almeida R, Tuerlings M, Suchiman HED, Broekhuis D, Nelissen RGHH, Ramos YFM, van Meurs JBJ and Meulenbelt I: Characterization of dynamic changes in matrix Gla protein (MGP) gene expression as function of genetic risk alleles, osteoarthritis relevant stimuli, and the vitamin K inhibitor warfarin. Osteoarthritis Cartilage. 29:1193–1202. 2021.

77 

Laurent C, Marano A, Baldit A, Ferrari M, Perrin JC, Perroud O, Bianchi A and Kempf H: A preliminary study exploring the mechanical properties of normal and Mgp-deficient mouse femurs during early growth. Proc Inst Mech Eng H. 236:1106–1117. 2022.

78 

Zhang J, Ma Z, Yan K, Wang Y, Yang Y and Wu X: Matrix Gla protein promotes the bone formation by up-regulating Wnt/β-catenin signaling pathway. Front Endocrinol (Lausanne). 10:8912019.

79 

Lanham SS, Cagampang FR and Oreffo ROC: Maternal high-fat diet and offspring expression levels of vitamin K-dependent proteins. Endocrinology. 155:4749–4761. 2014.

80 

Lanham SA, Cagampang FR and Oreffo ROC: The influence of a high fat diet on bone and soft tissue formation in Matrix Gla Protein knockout mice. Sci Rep. 8:36352018.

81 

Julien M, Khoshniat S, Lacreusette A, Gatius M, Bozec A, Wagner EF, Wittrant Y, Masson M, Weiss P, Beck L, et al: Phosphate-dependent regulation of MGP in osteoblasts: Role of ERK1/2 and Fra-1. J Bone Miner Res. 24:1856–1868. 2009.

82 

Zhang Y, Zhao L, Wang N, Li J, He F, Li X and Wu S: Unexpected role of matrix Gla protein in osteoclasts: Inhibiting osteoclast differentiation and bone resorption. Mol Cell Biol. 39:e00012–19. 2019.

83 

Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR and Karsenty G: Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 386:78–81. 1997.

84 

Julien M, Magne D, Masson M, Rolli-Derkinderen M, Chassande O, Cario-Toumaniantz C, Cherel Y, Weiss P and Guicheux J: Phosphate stimulates matrix Gla protein expression in chondrocytes through the extracellular signal regulated kinase signaling pathway. Endocrinology. 148:530–537. 2007.

85 

Zandueta C, Ormazábal C, Perurena N, Martínez-Canarias S, Zalacaín M, Julián MS, Grigoriadis AE, Valencia K, Campos-Laborie FJ, Rivas Jde L, et al: Matrix-Gla protein promotes osteosarcoma lung metastasis and associates with poor prognosis. J Pathol. 239:438–449. 2016.

86 

Willeit K, Santer P, Tschiderer L, Pechlaner R, Vermeer C, Willeit J and Kiechl S: Association of desphospho-uncarboxylated matrix gla protein with incident cardiovascular disease and all-cause mortality: Results from the prospective Bruneck study. Atherosclerosis. 353:20–27. 2022.

87 

Malhotra R, Nicholson CJ, Wang D, Bhambhani V, Paniagua S, Slocum C, Sigurslid HH, Lino Cardenas CL, Li R, Boerboom SL, et al: Matrix Gla protein levels are associated with arterial stiffness and incident heart failure with preserved ejection fraction. Arterioscler Thromb Vasc Biol. 42:e61–e73. 2022.

88 

Parashar A, Bak K and Murshed M: Prevention of arterial elastocalcinosis: Differential roles of the conserved glutamic acid and serine residues of matrix Gla protein. Arterioscler Thromb Vasc Biol. 42:e155–e167. 2022.

89 

Gheorghe SR, Vermeer C, Olteanu G, Silaghi CN and Crăciun AM: The active isoforms of MGP are expressed in healthy and varicose veins without calcification. J Clin Med. 10:58962021.

90 

Chiyoya M, Seya K, Yu Z, Daitoku K, Motomura S, Imaizumi T, Fukuda I and Furukawa KI: Matrix Gla protein negatively regulates calcification of human aortic valve interstitial cells isolated from calcified aortic valves. J Pharmacol Sci. 136:257–265. 2018.

91 

Lu X, Gao B, Liu Z, Tian X, Mao X, Emmanuel N, Zhu Q and Xiao C: A polymorphism of matrix Gla protein gene is associated with kidney stone in the Chinese Han population. Gene. 511:127–130. 2012.

92 

Gao B, Yasui T, Itoh Y, Tozawa K, Hayashi Y and Kohri K: A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol. 177:2361–2365. 2007.

93 

Lu X, Gao B, Yasui T, Li Y, Liu T, Mao X, Hirose M, Wu Y, Yu D, Zhu Q, et al: Matrix Gla protein is involved in crystal formation in kidney of hyperoxaluric rats. Kidney Blood Press Res. 37:15–23. 2013.

94 

Goiko M, Dierolf J, Gleberzon JS, Liao Y, Grohe B, Goldberg HA, de Bruyn JR and Hunter GK: Peptides of matrix Gla protein inhibit nucleation and growth of hydroxyapatite and calcium oxalate monohydrate crystals. PLoS One. 8:e803442013.

95 

Castiglione V, Pottel H, Lieske JC, Lukas P, Cavalier E, Delanaye P and Rule AD: Evaluation of inactive matrix-Gla-Protein (MGP) as a biomarker for incident and recurrent kidney stones. J Nephrol. 33:101–107. 2020.

96 

Viegas CS, Simes DC, Laizé V, Williamson MK, Price PA and Cancela ML: Gla-rich protein (GRP), a new vitamin K-dependent protein identified from sturgeon cartilage and highly conserved in vertebrates. J Biol Chem. 283:36655–3664. 2008.

97 

Le Jeune M, Tomavo N, Tian TV, Flourens A, Marchand N, Camuzeaux B, Mallein-Gerin F and Duterque-Coquillaud M: Identification of four alternatively spliced transcripts of the Ucma/GRP gene, encoding a new Gla-containing protein. Exp Cell Res. 316:203–215. 2010.

98 

Tagariello A, Luther J, Streiter M, Didt-Koziel L, Wuelling M, Surmann-Schmitt C, Stock M, Adam N, Vortkamp A and Winterpacht A: Ucma-A novel secreted factor represents a highly specific marker for distal chondrocytes. Matrix Biol. 27:3–11. 2008.

99 

Cancela ML, Conceição N and Laizé V: Gla-rich protein, a new player in tissue calcification? Adv Nutr. 3:174–181. 2012.

100 

Conceição N, Fazenda C and Cancela ML: Comparative gene promoter analysis: An in silico strategy to identify candidate regulatory factors for Gla rich protein. J Appl Ichthyol. 28:372–376. 2012.

101 

Viegas CS, Cavaco S, Neves PL, Ferreira A, João A, Williamson MK, Price PA, Cancela ML and Simes DC: Gla-rich protein is a novel vitamin K-dependent protein present in serum that accumulates at sites of pathological calcifications. Am J Pathol. 175:2288–2298. 2009.

102 

Viegas CS, Herfs M, Rafael MS, Enriquez JL, Teixeira A, Luís IM, van 't Hoofd CM, João A, Maria VL, Cavaco S, et al: Gla-rich protein is a potential new vitamin K target in cancer: Evidences for a direct GRP-mineral interaction. Biomed Res Int. 2014:3402162014.

103 

Neacsu CD, Grosch M, Tejada M, Winterpacht A, Paulsson M, Wagener R and Tagariello A: Ucmaa (Grp-2) is required for zebrafish skeletal development. Evidence for a functional role of its glutamate γ-carboxylation. Matrix Biol. 30:369–378. 2011.

104 

Lee YJ, Park SY, Lee SJ, Boo YC, Choi JY and Kim JE: Ucma, a direct transcriptional target of Runx2 and Osterix, promotes osteoblast differentiation and nodule formation. Osteoarthritis Cartilage. 23:1421–1431. 2015.

105 

Lee YJ, Ju HY, Park SY, Ihn HJ, Park EK and Kim JE: Recombinant unique cartilage matrix-associated protein potentiates osteogenic differentiation and mineralization of MC3T3-E1 cells. Curr Mol Med. 22:747–754. 2022.

106 

Cavaco S, Viegas CS, Rafael MS, Ramos A, Magalhães J, Blanco FJ, Vermeer C and Simes DC: Gla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis. Cell Mol Life Sci. 73:1051–1065. 2016.

107 

Bordoloi J, Dihingia A, Kalita J and Manna P: Implication of a novel vitamin K dependent protein, GRP/Ucma in the pathophysiological conditions associated with vascular and soft tissue calcification, osteoarthritis, inflammation, and carcinoma. Int J Biol Macromol. 113:309–316. 2018.

108 

Viegas CSB, Rafael MS, Enriquez JL, Teixeira A, Vitorino R, Luís IM, Costa RM, Santos S, Cavaco S, Neves J, et al: Gla-rich protein acts as a calcification inhibitor in the human cardiovascular system. Arterioscler Thromb Vasc Biol. 35:399–408. 2015.

109 

Willems BA, Furmanik M, Caron MMJ, Chatrou MLL, Kusters DHM, Welting TJM, Stock M, Rafael MS, Viegas CSB, Simes DC, et al: Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling. Sci Rep. 8:49612018.

110 

Viegas CSB, Santos L, Macedo AL, Matos AA, Silva AP, Neves PL, Staes A, Gevaert K, Morais R, Vermeer C, et al: Chronic kidney disease circulating calciprotein particles and extracellular vesicles promote vascular calcification: A role for GRP (Gla-rich protein). Arterioscler Thromb Vasc Biol. 38:575–587. 2018.

111 

Viegas CSB, Araújo N, Carreira J, Pontes JF, Macedo AL, Vinhas M, Moreira AS, Faria TQ, Grenha A, de Matos AA, et al: Nanoencapsulation of Gla-rich protein (GRP) as a novel approach to target inflammation. Int J Mol Sci. 23:48132022.

112 

Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H and Mizuno K: Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem. 271:30022–30027. 1996.

113 

Muñoz X, Sumoy L, Ramírez-Lorca R, Villar J, de Frutos PG and Sala N: Human vitamin K-dependent GAS6: Gene structure, allelic variation, and association with stroke. Hum Mutat. 23:506–512. 2004.

114 

Zhu C, Wei Y and Wei X: AXL receptor tyrosine kinase as a promising anti-cancer approach: Functions, molecular mechanisms and clinical applications. Mol Cancer. 18:1532019.

115 

Nakamura YS, Hakeda Y, Takakura N, Kameda T, Hamaguchi I, Miyamoto T, Kakudo S, Nakano T, Kumegawa M and Suda T: Tyro 3 receptor tyrosine kinase and its ligand, Gas6, stimulate the function of osteoclasts. Stem Cells. 16:229–238. 1998.

116 

Hutchison MR, Bassett MH and White PC: SCF, BDNF, and Gas6 are regulators of growth plate chondrocyte proliferation and differentiation. Mol Endocrinol. 24:193–203. 2010.

117 

Sweeney MD, Ayyadurai S and Zlokovic BV: Pericytes of the neurovascular unit: Key functions and signaling pathways. Nat Neurosci. 19:771–783. 2016.

118 

Collett G, Wood A, Alexander MY, Varnum BC, Boot-Handford RP, Ohanian V, Ohanian J, Fridell YW and Canfield AE: Receptor tyrosine kinase Axl modulates the osteogenic differentiation of pericytes. Circ Res. 92:1123–1129. 2003.

119 

Son BK and Akishita M: Vascular calcification and anti-aging. Clin Calcium. 18:912–917. 2008.In Japanese.

120 

Nanao-Hamai M, Son BK, Hashizume T, Ogawa S and Akishita M: Protective effects of estrogen against vascular calcification via estrogen receptor α-dependent growth arrest-specific gene 6 transactivation. Biochem Biophys Res Commun. 480:429–435. 2016.

121 

Srinath R, Gottesman RF, Hill Golden S, Carson KA and Dobs A: Association between endogenous testosterone and cerebrovascular disease in the ARIC study (atherosclerosis risk in communities). Stroke. 47:2682–2688. 2016.

122 

Son BK, Akishita M, Iijima K, Ogawa S, Maemura K, Yu J, Takeyama K, Kato S, Eto M and Ouchi Y: Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification. J Biol Chem. 285:7537–7544. 2010.

123 

Qiu C, Zheng H, Tao H, Yu W, Jiang X, Li A, Jin H, Lv A and Li H: Vitamin K2 inhibits rat vascular smooth muscle cell calcification by restoring the Gas6/Axl/Akt anti-apoptotic pathway. Mol Cell Biochem. 433:149–159. 2017.

124 

Kraler S, Blaser MC, Aikawa E, Camici GG and Lüscher TF: Calcific aortic valve disease: From molecular and cellular mechanisms to medical therapy. Eur Heart J. 43:683–697. 2022.

125 

Kim H, Kim HJ, Lee K, Kim JM, Kim HS, Kim JR, Ha CM, Choi YK, Lee SJ, Kim JY, et al: α-Lipoic acid attenuates vascular calcification via reversal of mitochondrial function and restoration of Gas6/Axl/Akt survival pathway. J Cell Mol Med. 16:273–286. 2012.

126 

Hu L, Ji J, Li D, Meng J and Yu B: The combined effect of vitamin K and calcium on bone mineral density in humans: A meta-analysis of randomized controlled trials. J Orthop Surg Res. 16:5922021.

127 

Huang SW, Xiang DK, Wu HL, Chen BL, An BQ and Li GF: Impact of five genetic polymorphisms on inter-individual variation in warfarin maintenance dose. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 28:661–665. 2011.In Chinese.

128 

Yuan HY, Chen JJ, Lee MT, Wung JC, Chen YF, Charng MJ, Lu MJ, Hung CR, Wei CY, Chen CH, et al: A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum Mol Genet. 14:1745–1751. 2005.

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Spandidos Publications style
Zhang M, Zhang Q, Du P, Chen X and Zhang Y: Roles of vitamin K‑dependent protein in biomineralization (Review). Int J Mol Med 53: 6, 2024.
APA
Zhang, M., Zhang, Q., Du, P., Chen, X., & Zhang, Y. (2024). Roles of vitamin K‑dependent protein in biomineralization (Review). International Journal of Molecular Medicine, 53, 6. https://doi.org/10.3892/ijmm.2023.5330
MLA
Zhang, M., Zhang, Q., Du, P., Chen, X., Zhang, Y."Roles of vitamin K‑dependent protein in biomineralization (Review)". International Journal of Molecular Medicine 53.1 (2024): 6.
Chicago
Zhang, M., Zhang, Q., Du, P., Chen, X., Zhang, Y."Roles of vitamin K‑dependent protein in biomineralization (Review)". International Journal of Molecular Medicine 53, no. 1 (2024): 6. https://doi.org/10.3892/ijmm.2023.5330
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang M, Zhang Q, Du P, Chen X and Zhang Y: Roles of vitamin K‑dependent protein in biomineralization (Review). Int J Mol Med 53: 6, 2024.
APA
Zhang, M., Zhang, Q., Du, P., Chen, X., & Zhang, Y. (2024). Roles of vitamin K‑dependent protein in biomineralization (Review). International Journal of Molecular Medicine, 53, 6. https://doi.org/10.3892/ijmm.2023.5330
MLA
Zhang, M., Zhang, Q., Du, P., Chen, X., Zhang, Y."Roles of vitamin K‑dependent protein in biomineralization (Review)". International Journal of Molecular Medicine 53.1 (2024): 6.
Chicago
Zhang, M., Zhang, Q., Du, P., Chen, X., Zhang, Y."Roles of vitamin K‑dependent protein in biomineralization (Review)". International Journal of Molecular Medicine 53, no. 1 (2024): 6. https://doi.org/10.3892/ijmm.2023.5330
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