Abstract
Zinc is known as an essential nutritional factor in the growth of the human and animals. Bone growth retardation is a common finding in various conditions associated with dietary zinc deficiency. Bone zinc content has been shown to decrease in aging, skeletal unloading, and postmenopausal conditions, suggesting its role in bone disorder. Zinc has been demonstrated to have a stimulatory effect on osteoblastic bone formation and mineralization; the metal directly activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational process of protein synthesis, in the cells, and it stimulates cellular protein synthesis. Zinc has been shown to stimulate gene expression of the transcription factors runt-related transcription factor 2 (Runx2) that is related to differentiation into osteoblastic cells. Moreover, zinc has been shown to inhibit osteoclastic bone resorption due to inhibiting osteoclast-like cell formation from bone marrow cells and stimulating apoptotic cell death of mature osteoclasts. Zinc has a suppressive effect on the receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclastogenesis. Zinc transporter has been shown to express in osteoblastic and osteoclastic cells. Zinc protein is involved in transcription. The intake of dietary zinc causes an increase in bone mass. β-Alanyl-l-histidinato zinc (AHZ) is a zinc compound, in which zinc is chelated to β-alanyl-l-histidine. The stimulatory effect of AHZ on bone formation is more intensive than that of zinc sulfate. Zinc acexamate has also been shown to have a potent-anabolic effect on bone. The oral administration of AHZ or zinc acexamate has the restorative effect on bone loss under various pathophysiologic conditions including aging, skeletal unloading, aluminum bone toxicity, calcium- and vitamin D-deficiency, adjuvant arthritis, estrogen deficiency, diabetes, and fracture healing. Zinc compounds may be designed as new supplementation factor in the prevention and therapy of osteoporosis.
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References
Prasad AS, Halsted JA, Nadimi M (1961) Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia. Am J Med 31:532–546
Burch RE, Hahn HK, Sullivan JF (1975) Newer aspects of the roles of zinc, manganese, and copper in human nutrition. Clin Chem 21:501–520
Parisi AF, Vallee BL (1969) Zinc metalloenzyme: characteristic and significance in biology and medicine. Am J Clin Nutr 22:1222–1230
Hsieh HS, Navia JM (1980) Zinc deficiency and bone formation in guinea pig alveolar implants. J Nutr 110:1581–1588
Oner G, Bhaumick B, Bala RM (1984) Effect of zinc deficiency on serum somatomedin levels and skeletal growth in young rats. Endocrinology 114:1860–1863
Hurley LS (1981) Tetratogenic aspects of manganese, zinc, and copper nutrition. Physiol Rev 61:249–295
da Cunha Ferreira RM, Marguiegui IM, Elizaga IV (1989) Tetratogenicity of zinc deficiency in the rat: study of the fetal skeleton. Tetratology 39:181–194
Leek JC, Vogler JB, Gershwin ME, Golub MS, Hurley LS, Hendrickx AG (1984) Studies of marginal zinc deprivation in rhesus monkeys. V. Fetal and infant skeletal defects. Am J Clin Nutr 40:1203–1212
Ronaghy HA, Reinhold JG, Mahloudji M, Ghavami P, Spirey Fox MR, Halstead JA (1984) Zinc supplementation of malnourished schoolboys in Iran: increased growth and other effects. Am J Clin Nutr 40:1203–1212
Herzberg M, Foldes J, Steinberg R, Menczel J (1990) Zinc excretion in osteoporotic women. J Bone Miner Res 5:251–257
Haumont S (1961) Distribution of zinc in bone tissues. J Histochem Cytochem 9:141–145
Hurley LS, Shyy-Hwa T (1972) Alleviation of tetratogenic effects of zinc deficiency by simultaneous lack of calcium. Am J Phys 222:322–325
Masters DG, Keen CL, Lonnerdal B, Hurley LS (1986) Release of zinc from maternal tissues during zinc deficiency or simultaneous zinc and calcium deficiency in the pregnant rat. J Nutr 116:2148–2154
Murray EJ, Messer HH (1981) Turnover of bone zinc during normal and accelerated bone loss in rats. J Nutr 111:1641–1647
Sherman SS, Smith JC, Tobin JD, Soares JH (1989) Ovariectomy, dietary zinc, and bone metabolism in retired breeder rats. Am J Clin Nutr 49:1184–1191
Aitken JM (1976) Factors affecting the distribution of zinc in the human skeleton. Calcif Tissue Res 20:23–30
Sauer GR, Wuthier RE (1990) Distribution of zinc in the avian growth plate. J Bone Miner Res 5(Suppl 2):S162
Lappalainer R, Knuuttila M, Lammi S, Alhava EM (1983) Fluoride content related to the elemental composition, mineral density and strength of bone in healthy and chronically diseased persons. J Chronic Dis 36:707–713
Reginster JY, Strause LG, Saltman O, Franchimont P (1988) Trace elements and postmenopausal osteoporosis: a preliminary study of decreased serum manganese. Med Sci Res 16:337–338
Saltman P, Strause L (1991) Trace elements in bone metabolism. J Inorg Biochem 43:284 (abstract)
Parfitt AM (1990) Bone-forming cells in clinical conditions. In: Hall BK (ed) Bone volume 1. The osteoblast and osteocyte. Telford Press/CRC Press, Boca Raton, pp 351–429
Baron R, Vignery A, Horowitz M (1984) Lymphocytes, macrophages and the regulation of bone remodeling. Bone Miner Res 2:175–243
Canalis E, McCarthy T, Centrella M (1988) Growth factors and the regulation of bone remodeling. J Clin Invest 81:277–281
Yamaguchi M, Takahashi K (1984) Role of zinc as an activator of bone metabolism in weanling rats. Jpn J Bone Metab 2:186–191
Yamaguchi M, Inamoto K, Suketa Y (1986) Effect of essential trace metals on bone metabolism in weanling rats: comparison with zinc and other metals’ actions. Res Exp Med 186:337–342
Yamaguchi M, Uchiyama M (1987) Preventive effect of zinc for toxic actions of germanium and selenium on bone metabolism in weanling rats. Res Exp Med 187:395–400
Lai YL, Yamaguchi M (2005) Effects of copper on bone component in the femoral tissues of rats: anabolic effect of zinc is weakened by copper. Biol Pharm Bull 28:2296–2301
Yamaguchi M, Osishi H, Suketa Y (1987) Stimulatory effect of zinc on bone formation in tissue culture. Biochem Pharmacol 36:4007–4012
Yamaguchi M, Oishi H, Suketa Y (1988) Zinc stimulation of bone protein synthesis in tissue culture. Activation of aminoacyl-tRNA synthetase. Biochem Pharmacol 37:4075–4080
Yamaguchi M, Matsui R (1989) Effect of dipicolinate, a chelator of zinc, on bone protein synthesis in tissue culture. The essential role of zinc. Biochem Pharmacol 38:4485–4489
Shimokawa N, Yamaguchi M (1992) Characterization of bone protein components with polyacrylamide gel electrophoresis: effects of zinc and hormones in tissue culture. Mol Cell Biochem 117:153–158
Yamaguchi M, Sakashita T (1986) Enhancement of vitamin D3 effect on bone metabolism in weanling rats orally administered zinc sulphate. Acta Endocrinol 111:285–288
Yamaguchi M, Yamaguchi R (1986) Action of zinc on bone metabolism in rats. Increase in alkaline phosphatase activity and DNA content. Biochem Pharmacol 35:773–777
Yamaguchi M, Inamoto K (1986) Differential effects of calcium-regulating hormones on bone metabolism in weanling rats orally administered zinc sulfate. Metabolism 35:1044–1047
McDonnell DP, Mongelsdorf DJ, Pike JW, Haussler MR, O’Malley BW (1987) Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. Science 235:1214–1217
Yamaguchi M, Oishi H (1989) Effect of 1, 25-dihydroxyvitamin D3 on bone metabolism in tissue culture. Enhancement of this steroid effect by zinc. Biochem Pharmacol 38:3453–3459
Yamaguchi M, Kitajima T (1991) Effect of estrogen on bone metabolism in tissue culture: enhancement of the steroid effect by zinc. Res Exp Med 191:145–154
Lutz W, Burritt MF, Nixon DE, Kao PC, Kumar R (2000) Zinc increases the activity of vitamin D-dependent promoters in osteoblasts. Biochem Biophys Res Commun 271:1–7
Hashizume M, Yamaguchi M (1993) Stimulatory effect of β-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells. Mol Cell Biochem 122:59–64
Hashizume M, Yamaguchi M (1994) Effect of β-alanyl-L-histidinato zinc on differentiation of osteoblastic MC3T3-E1 cells: increases in alkaline phosphatase activity and protein concentration. Mol Cell Biochem 131:19–24
Yamaguchi M, Hashizume M (1994) Effect of β-alanyl-L-histidinato zinc on protein components in osteoblastic MC3T3-E1 cells: increases in osteocalcin, insulin-like growth factor-I and transforming growth factor-β. Mol Cell Biochem 136:163–169
Matsui T, Yamaguchi M (1995) Zinc modulation of insulin-like growth factor’s effect in osteoblastic MC3T3-E1 cells. Peptides 16:1063–1068
Yamaguchi M, Fukagawa M (2005) Role of zinc in regulation of protein tyrosine phosphatase activity in osteoblastic MC3T3-E1 cells: zinc modulation of insulin-like growth factor-I’s effect. Calcif Tissue Int 76:32–38
Yamaguchi M, Kishi S, Hashizume M (1994) Effect of zinc-chelating dipeptides on osteoblastic MC3T3-E1 cells: activation of aminoacyl-tRNA synthetase. Peptides 15:1367–1371
Yamaguchi M, Matsui T (1996) Stimulatory effect of zinc-chelating dipeptide on deoxyribonucleic acid synthesis in osteoblastic MC3T3-E1 cells. Peptide 17:1207–1211
Yamaguchi M, Goto M, Uchiyama S, Nakagawa T (2008) Effect of zinc on gene expression in osteoblastic MC3T3-E1 cells: enhancement of Runx2, OPG, and regucalcin mRNA expressions. Mol Cell Biochem 312:157–166
Yamaguchi M, Segawa Y, Shimokawa N, Tsuzuike N, Tagashira E (1992) Inhibitory effect of β-alanyl-L-histidinato zinc on bone resorption in tissue culture. Pharmacology 45:292–300
Yamaguchi M, Hashizume M (1994) Effect of parathyroid hormone and interleukin-1α in osteoblastic MC3T3-E1 cells: interaction with β-alanyl-L-histidinato zinc. Peptides 15:633–636
Kishi S, Yamaguchi M (1994) Inhibitory effect of zinc compounds on osteoclast-like cell formation in mouse marrow cultures. Biochem Pharmacol 48:1225–1230
Yamaguchi M, Kishi S (1996) Zinc compounds inhibit osteoclast-like cell formation at the earlier stage of rat marrow culture but not osteoclast function. Mol Cell Biochem 158:171–177
Yamaguchi M, Kishi S (1995) Inhibitory effect of zinc-chelating dipeptide on parathyroid hormone-stimulated osteoclast-like cell formation in mouse marrow cultures: involvement of calcium signaling. Peptides 16:629–633
Zaidi M, Blair HC, Moonga BS, Abe E, Huang CL-H (2003) Osteoclastogenesis, bone resorption, and osteoclast-based therapeutics. J Bone Miner Res 18:599–609
Asagiri M, Takayanagi H (2007) The molecular understanding of osteoclast differentiation. Bone 40:251–264
Anderson DM, Marashovsky E, Billingoley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L (1997) A homologue of the TNF receptor and its ligand enhances T-cell growth an dentritic-cell function. Nature (London) 390:175–179
Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95:3597–3602
Tsuda E, Goto M, Mochizuki S, Yano K, Kobayashi F, Morinaga T, Higashio K (1997) Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Commun 234:137–142
Inoue J, Ishida T, Tsukamoto N, Kobayashi N, Naito A, Azuma S, Yamamoto T (2000) Tumor necrosis factor receptor-associated factor (TRAF) family: adaptor proteins that mediate cytokine signaling. Exp Cell Res 254:14–24
Yamaguchi M, Uchiyma S (2004) Receptor activator of Nf-κB ligand (RANKL)-stimulated osteoclastogenesis in mouse marrow culture is suppressed by zinc in vitro. Int J Mol Med 14:81–85
Zou W, Hikim I, Tschoep K, Endres S, Zvi B-S (2001) Tumor necrosis factor-mediated RANK ligand stimulation of osteoclast differentiation by an autocrine mechanism. J Cell Biochem 83:70–83
Ma ZJ, Yamaguchi M (2000) Alteration in bone components with increasing age of newborn rats: role of zinc in bone growth. J Bone Miner Metab 18:264–270
Ma ZJ, Yamaguchi M (2001) Role of endogenous zinc in the enhancement of bone protein synthesis associated with bone growth of newborn rats. J Bone Miner Metab 19:38–44
Ma ZJ, Misawa H, Yamaguchi M (2001) Stimulatory effect of zinc on insulin-like growth factor-I and transforming growth factor-β1 production with bone growth of newborn rats. Int J Mol Med 8:623–628
Gabbitas B, Pash J, Canalis E (1994) Regulation of insulin-like growth factor-II synthesis in bone cell cultures by skeletal growth factors. Endocrinology 135:284–289
Asahina I, Sampath TK, Nishimura I, Hauschka PV (1999) Human osteogenic protein-1 induces both chondroblastic and osteoblastic differentiation of osteoprogenitor cells derived from newborn rat calvaria. J Cell Biol 123:921–933
Ma ZJ, Yamaguchi M (2001) Stimulatory effect of zinc and growth factor on bone protein component in newborn rats: enhancement with zinc and insulin-like growth factor-I. Int J Mol Med 7:73–78
Ma ZJ, Yamaguchi M (2001) Stimulatory effect of zinc on deoxyribonucleic acid synthesis in bone growth of newborn rats: enhancement with zinc and insulin-like growth factor-I. Calcif Tissue Int 69:158–163
Barnes GL, Kostenuik PJ, Gerstenfeld LC, Eihorn TA (1999) Growth factor regulation of fracture repair. J Bone Miner Res 14:1805–1815
Eihorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop 355S:S7–S21
Bolander ME (1998) Regulation of fracture repair by growth factors. Proc Soc Exp Biol Med 200:165–170
Igarashi A, Yamaguchi M (1999) Increase in bone protein components with healing rat fractures: enhancement by zinc treatment. Int J Mol Med 4:615–620
Igarashi A, Yamaguchi M (2001) Increase in bone growth factors with healing rat fractures: the enhancing effect of zinc. Int J Mol Med 8:433–438
Igarashi A, Yamaguchi M (2002) Characterization of the increase in bone 66 kDa protein component with healing rat fractures: stimulatory effect of zinc. Int J Mol Med 9:503–508
Igarashi A, Yamaguchi M (2003) Great increase in bone 66 kDa protein and osteocalcin at later stage with healing rat fractures: effect of zinc treatment. Int J Mol Med 11:223–228
Yamaguchi M, Igarashi A, Misawa H, Tsurusaki Y (2003) Enhancement of albumin expression in bone tissues with healing rat fractures. J Cell Biochem 89:356–363
Ishida K, Sawada N, Yamaguchi M (2004) Expression of albumin in bone tissues and osteoblastic cells: involvement of hormone regulation. Int J Mol Med 14:891–895
Ishida K, Yamaguchi M (2004) Role of albumin in osteoblastic cells: enhancement of cell proliferation and suppression of alkaline phosphatase activity. Int J Mol Med 14:1077–1081
Ishida K, Yamaguchi M (2005) Albumin regulates Runx2 and α1 (I) collagen mRNA expression in osteoblastic cells: comparison with insulin-like growth factor-I. Int J Mol Med 16:689–694
Igarashi A, Yamaguchi M (1999) Stimulatory effect of zinc acexamate administration on fracture healing of the femoral-diaphyseal tissues in rats. Gen Pharmacol 32:463–469
Yamaguchi M, Ozaki K (1990) A new zinc compound, β-alanyl-L-histidinato zinc, stimulates bone growth in weanling rats. Res Exp Med 190:105–110
Yamaguchi M, Miwa H (1991) Stimulatory effect of beta-alanyl-L-histidinato zinc on bone formation in tissue culture. Pharmacology 42:230–240
Samuchson J (1967) Mechanism for the exchange of the calcium in bone mineral. Nature 216:193–194
Yamaguchi M, Ohtaki J (1991) Effect of beta-alanyl-L-histidinato zinc on osteoblastic MC3T3-E1 cells: increases in alkaline phosphatase and proliferation. Pharmacology 43:225–232
Yamaguchi M, Kishi S (1994) Effect of zinc-chelating dipeptide on bone metabolism in weanling rats: comparison with β-alanyl-L-histidinato zinc-related compounds. Peptides 15:671–673
Yamaguchi M, Kishi S (1994) Comparison of the effect of β-alanyl-L-histidinato zinc and its zinc-chelating ligand on bone metabolism in tissue culture. Biol Pharm Bull 17:522–526
Yamaguchi M, Ozaki K, Suketa Y (1989) Alteration in bone metabolism with increasing age: Effects of zinc and vitamin D3 in aged rats. J Pharmacobio-Dyn 12:67–73
Yamaguchi M, Ozaki K (1990) Aging affects cellular zinc and protein synthesis in the femoral diaphysis of rats. Res Exp Med 190:295–300
Yamaguchi M, Ozaki K (1990) Effect of the new zinc compound beta-alanyl-L-histidinato zinc on bone metabolism in elderly rats. Pharmacology 41:345–349
Kishi S, Yamaguchi M (1994) Stimulatory effect of β-alanyl-L-histidinato zinc on alkaline phosphatase activity in bone tissue from elderly rats: comparison with zinc sulfate action. Biol Pharm Bull 17:345–347
Yamaguchi M, Ehara Y (1995) Zinc decrease and bone metabolism in the femoral-metaphyseal tissues of rats with skeletal unloading. Calcif Tissue Int 57:218–223
Yamaguchi M, Ehara Y (1996) Effect of essential trace metal on bone metabolism in the femoral-metaphyseal tissues of rats with skeletal unloading: comparison with zinc-chelating dipeptide. Calcif Tissue Int 59:27–32
Morey ER, Baylink DJ (1978) Inhibition of bone formation during spaceflight. Science 201:1138–1141
Yamaguchi M, Ozaki K, Hoshi T (1990) β-Alanyl-L-histidinato zinc prevents skeletal unloading-induced disorder of bone metabolism in rats. Res Exp Med 190:289–294
Maloney NA, Ott SM, Alfrey AC, Miller NL, Coburn JW, Sherrard DJ (1982) Histological quantitation of aluminium in iliac from patients with renal failure. J Lab Clin Med 99:206–216
Yamaguchi M, Ozaki K (1990) Beta-alanyl-L-histidinato zinc prevents the toxic effect of aluminium on bone metabolism in weanling rats. Pharmacology 41:338–344
Segawa Y, Tsuzuike N, Tagashira E, Yamaguchi M (1992) Preventive effect of β-alanyl-L-histidinato zinc on bone metabolism in rats fed on low-calcium and vitamin D-deficient diets. Res Exp Med 192:213–219
Segawa Y, Tsuzuike N, Itokazu Y, Tagashira E, Yamaguchi M (1993) Effect of β-alanyl-L-histidinato zinc on bone metabolism in rats with adjuvant arthritis. Biol Pharm Bull 16:656–659
Sugiyama T, Tanaka H, Kawai S (2000) Improvement of periarticular osteoporosis in postmenopausal women with rheumatoid arthritis by beta-alanyl-L-histidinato zinc: a pilot study. J Bone Miner Metab 18:335–338
Pock WA (1984) The effects of glucocorticoids on bone cell metabolism and function. Adv Exp Med Biol 171:111–119
Segawa Y, Tsuzuike N, Itokazu Y, Tagashira E, Yamaguchi M (1992) β-Alanyl-L-histidinato zinc prevents hydrocortisone-induced disorder of bone metabolism in rats. Res Exp Med 192:317–322
Johnston CC Jr, Hui SL, Witt RM, Appledonn R, Baker RS, Longcope C (1985) Early menopausal changes in bone mass and sex steroids. J Clin Endocrinol Metab 61:905–911
Goulding A, Gold E (1987) Effects of chronic prednisolone treatment on bone resorption and bone composition in intact and ovariectomized rats receiving β-estradiol. Endocrinology 122:482–487
Segawa Y, Tsuzuike N, Tagashira E, Yamaguchi M (1993) Preventive effect of β-alanyl-L-histidinato zinc on the deterioration of bone metabolism in ovariectomized rats. Biol Pharm Bull 16:486–489
Yamaguchi M, Kishi S (1993) Prolonged administration of β-alanyl-L-histidinato zinc prevents bone loss in ovariectomized rats. Jpn J Pharmacol 63:203–207
Kishi S, Segawa Y, Yamaguchi M (1994) Histomorphological confirmation of the preventive effect of β-alanyl-L-histidinato zinc on bone loss in ovariectomized rats. Biol Pharm Bull 17:862–865
Yamaguchi M, Gao YH (1998) Potent effect of zinc acexamate on bone components in the femoral-metaphyseal tissues of elderly female rats. Gen Pharmacol 30:423–427
Hui SL, Epstein S, Johanston CC (1985) A prospective study of bone mass in patients with type I diabetes. J Clin Endocrinol Metab 60:74–80
Mcnair P (1988) Bone mineral metabolism in human type I diabetes mellitus. Dan Med Bull 35:109–121
Yamaguchi M, Uchiyama S (2003) Preventive effect of zinc acexamate administration in streptozotocin-diabetic rats: restoration of bone loss. Int J Mol Med 12:755–761
Uchiyama S, Yamaguchi M (2003) Alteration in serum and bone component findings induced in streptozotocin-diabetic rats is restored by zinc acexamate. Int J Mol Med 12:949–954
Relea P, Revilla M, Ripoll E, Arribas I, Villa LF, Rico H (1995) Zinc, biochemical markers of nutrition, and type I osteoporosis. Age Ageing 24:303–307
Gur A, Colpan L, Cevik R, Nas K, Jale Sarac A (2005) Comparison of zinc excretion and biochemical markers of bone remodelling in the assessment of the effects of alendronate and calcitonin on bone in postmenopausal osteoporosis. Clin Biochem 38:66–72
Hill T, Meunier N, Andriollo-Sanchez M, Ciarapica D, Hininger-Favier I, Poloto A, O’Connor JM, Coudray C, Cashman KD (2005) The relationship between the zinc nutritive status and biochemical markers of bone turnover in older European adults: the ZENITH study. Eur J Clin Nutr 59(Suppl 2):S73–S78
Hyun TH, Barrett-Connor E, Milne DB (2004) Zinc intakes and plasma concentrations in men with osteoporosis: the Rancho Bermardo Study. Am J Clin Nutr 80:715–721
Rodondi A, Ammann P, Ghilardi-Beuret S, Rizzoli R (2009) Zinc increases the effects of essential amino acids–whey protein supplements in frail elderly. J Nutr Health Aging 13:491–497
Yamaguchi M, Igarashi A, Sakai M, Degawa H, Ozawa Y (2005) Prolonged intake of dietary fermented isoflavone-rich soybean reinforced with zinc affects circulating bone biochemical markers in aged individuals. J Health Sci 51:191–196
Yamaguchi M (1995) β-Alanyl-L-histidinato zinc: a potent activator in bone formation. Curr Med Chem 1:356–365
Yamaguchi M (1995) β-Alanyl-L-histidinato zinc and bone resorption. Gen Pharmacol 26:1179–1183
Yamaguchi M (1998) Role of zinc in bone formation and bone resorption. J Trace Elem Exp Med 11:119–135
Inoue K, Matsuda K, Itoh M, Kawaguchi H, Tomoike H, Aoyagi T, Nagai R, Hori M, Nakamura Y, Tanaka T (2002) Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5. Hum Mol Genet 15:1775–1784
Khadeer MA, Sahu SN, Bai G, Abdulla S, Gupta A (2005) Expression of the zinc transporter ZIP1 in osteoclasts. Bone 37:296–304
Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29
Shen ZJ, Nakamoto T, Tsuji K, Nifuji A, Miyazono K, Komori T, Hirai H, Noda M (2002) Negative regulation of bone morphogenetic protein/Smad signaling by Cas-interacting zinc finger protein in osteoblasts. J Biol Chem 277:29840–29846
Jones DC, Wein MN, Oukka M, Hofstaetter JG, Glimcher MJ, Glimcher LH (2006) Schnur regulation of adult bone mass by the zinc finger adapter protein ri-3. Science 312:1223–1227
Shin JN, Kim I, Lee JS, Koh GY, Lee ZH, Kim HH (2002) A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6. J Biol Chem 277:8346–8353
Yamaguchi M, Igarashi A, Uchiyama S (2004) Bioavailability of zinc yeast in rats: stimulatory effect on bone calcification in vivo. J Health Sci 50:75–81
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Yamaguchi, M. Role of nutritional zinc in the prevention of osteoporosis. Mol Cell Biochem 338, 241–254 (2010). https://doi.org/10.1007/s11010-009-0358-0
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DOI: https://doi.org/10.1007/s11010-009-0358-0