Skip to main content
Top
Published in: The journal of nutrition, health & aging 5/2017

01-05-2017

Bone degeneration and its recovery in SMP30/GNL-knockout mice

Authors: Kazutoshi Nishijima, T. Ohno, A. Amano, Y. Kishimoto, Y. Kondo, A. Ishigami, S. Tanaka

Published in: The journal of nutrition, health & aging | Issue 5/2017

Login to get access

Abstract

Senescence marker protein-30 (SMP30) decreases androgen-independently with aging and is a lactone-hydrolyzing enzyme gluconolactonase (GNL) that is involved in vitamin C biosynthesis. In the present study, bone properties of SMP30/GNL knockout (KO) mice with deficiency in vitamin C synthesis were investigated to reveal the effects of SMP30/GNL and exogenous vitamin C supplementation on bone formation. Mineral content (BMC) and mineral density (BMD) of the mandible and femur of SMP30/GNL KO and wild-type mice at 2 and 3 months of age with or without vitamin C supplementation were measured by dual-energy X-ray absorptiometry. Body and bone weight of both age groups decreased and became significantly lower than those of wild-type mice. The bones of SMP30/GNL KO mice were rough and porous, with BMC and BMD significantly below wild-type. Oral supplementation with vitamin C eliminated differences in body weight, bone weight, BMC, and BMD between SMP30/GNL KO and wild-type mice at each age. These results indicate that bone degeneration in SMP30/GNL KO mice was caused by lack of vitamin C, and that this mouse strain is an appropriate model for bone metabolism in humans, which have no ability to synthesize vitamin C.
Literature
2.
go back to reference Seeman E. Age-and menopause-related bone loss compromise cortical and trabecular microstructure. J Gerontol A Biol Sci Med Sci 2013;68:1218–1225. doi: 10.1093/gerona/glt071.CrossRefPubMed Seeman E. Age-and menopause-related bone loss compromise cortical and trabecular microstructure. J Gerontol A Biol Sci Med Sci 2013;68:1218–1225. doi: 10.1093/gerona/glt071.CrossRefPubMed
3.
go back to reference Langsetmo L, Barr SI, Berger C, Kreiger N, Rahme E, Adachi JD, Papaioannou A, Kaiser SM, Prior JC, Hanley DA, Kovacs CS, Josse RG, Goltzman D; CaMos Research Group. Associations of protein intake and protein source with bone mineral density and fracture risk: A population-based cohort study. J Nutr Health Aging 2015;19:861–8. doi: 10.1007/s12603-015-0544-6.CrossRefPubMedPubMedCentral Langsetmo L, Barr SI, Berger C, Kreiger N, Rahme E, Adachi JD, Papaioannou A, Kaiser SM, Prior JC, Hanley DA, Kovacs CS, Josse RG, Goltzman D; CaMos Research Group. Associations of protein intake and protein source with bone mineral density and fracture risk: A population-based cohort study. J Nutr Health Aging 2015;19:861–8. doi: 10.1007/s12603-015-0544-6.CrossRefPubMedPubMedCentral
4.
go back to reference Sotunde OF, Kruger HS, Wright HH, Havemann-Nel L, Kruger IM, Wentzel-Viljoen E, Kruger A, Tieland M. Lean mass appears to be more strongly associated with bone health than fat mass in urban black south African women. J Nutr Health Aging 2015;19:628–36. doi: 10.1007/s12603-015-0492-1.CrossRefPubMed Sotunde OF, Kruger HS, Wright HH, Havemann-Nel L, Kruger IM, Wentzel-Viljoen E, Kruger A, Tieland M. Lean mass appears to be more strongly associated with bone health than fat mass in urban black south African women. J Nutr Health Aging 2015;19:628–36. doi: 10.1007/s12603-015-0492-1.CrossRefPubMed
5.
6.
go back to reference Roughead ZK, Kunkel ME. Effect of diet on bone matrix constituents. J Am Coll Nutr 1991;10:242–246.CrossRefPubMed Roughead ZK, Kunkel ME. Effect of diet on bone matrix constituents. J Am Coll Nutr 1991;10:242–246.CrossRefPubMed
7.
go back to reference Kaptoge S, Welch A, McTaggart A, Mulligan A, Dalzell N, Day NE, Bingham S, Khaw KT, Reeve J. Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age. Osteoporos Int 2003;14:418–428.CrossRefPubMed Kaptoge S, Welch A, McTaggart A, Mulligan A, Dalzell N, Day NE, Bingham S, Khaw KT, Reeve J. Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age. Osteoporos Int 2003;14:418–428.CrossRefPubMed
8.
go back to reference Sahni S, Hannan MT, Gagnon D, Blumberg J, Cupples LA, Kiel DP, Tucker KL. Protective effect of total and supplemental vitamin C intake on the risk of hip fracture—a 17-year follow-up from the Framingham Osteoporosis Study. Osteoporos Int 2009;20:1853–1861. doi: 10.1007/s00198-009-0897-y.CrossRefPubMedPubMedCentral Sahni S, Hannan MT, Gagnon D, Blumberg J, Cupples LA, Kiel DP, Tucker KL. Protective effect of total and supplemental vitamin C intake on the risk of hip fracture—a 17-year follow-up from the Framingham Osteoporosis Study. Osteoporos Int 2009;20:1853–1861. doi: 10.1007/s00198-009-0897-y.CrossRefPubMedPubMedCentral
9.
go back to reference Talaulikar VS, Chambers T, Manyonda I. Exploiting the antioxidant potential of a common vitamin: could vitamin C prevent postmenopausal osteoporosis? J Obstet Gynaecol Res 2012;38:253–257. doi: 10.1111/j.1447-0756.2011.01629.x.CrossRefPubMed Talaulikar VS, Chambers T, Manyonda I. Exploiting the antioxidant potential of a common vitamin: could vitamin C prevent postmenopausal osteoporosis? J Obstet Gynaecol Res 2012;38:253–257. doi: 10.1111/j.1447-0756.2011.01629.x.CrossRefPubMed
10.
go back to reference Maruyama N, Ishigami A, Kondo Y. Pathophysiological significance of senescence marker protein-30. Geriatr Gerontol Int 2010;10 Suppl 1:S88–98. doi: 10.1111/j.1447-0594.2010.00586.x.CrossRefPubMed Maruyama N, Ishigami A, Kondo Y. Pathophysiological significance of senescence marker protein-30. Geriatr Gerontol Int 2010;10 Suppl 1:S88–98. doi: 10.1111/j.1447-0594.2010.00586.x.CrossRefPubMed
11.
go back to reference Kondo Y, Inai Y, Sato Y, Handa S, Kubo S, Shimokado K, Goto S, Nishikimi M, Maruyama N, Ishigami A. Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy. Proc Natl Acad Sci U S A 2006;103:5723–5728.CrossRefPubMedPubMedCentral Kondo Y, Inai Y, Sato Y, Handa S, Kubo S, Shimokado K, Goto S, Nishikimi M, Maruyama N, Ishigami A. Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy. Proc Natl Acad Sci U S A 2006;103:5723–5728.CrossRefPubMedPubMedCentral
12.
go back to reference Ishigami A, Fujita T, Handa S, Shirasawa T, Koseki H, Kitamura T, Enomoto N, Sato N, Shimosawa T, Maruyama N. Senescence marker protein-30 knockout mouse liver is highly susceptible to tumor necrosis factor-α-and Fas-mediated apoptosis. Am J Pathol 2002;161:1273–1281.CrossRefPubMedPubMedCentral Ishigami A, Fujita T, Handa S, Shirasawa T, Koseki H, Kitamura T, Enomoto N, Sato N, Shimosawa T, Maruyama N. Senescence marker protein-30 knockout mouse liver is highly susceptible to tumor necrosis factor-α-and Fas-mediated apoptosis. Am J Pathol 2002;161:1273–1281.CrossRefPubMedPubMedCentral
13.
go back to reference Kondo Y, Sasaki T, Sato Y, Amano A, Aizawa S, Iwama M, Handa S, Shimada N, Fukuda M, Akita M, Lee J, Jeong KS, Maruyama N, Ishigami A. Vitamin C depletion increases superoxide generation in brains of SMP30/GNL knockout mice. Biochem Biophys Res Commun 2008;377:291–296. doi: 10.1016/j.bbrc.2008.09.132.CrossRefPubMed Kondo Y, Sasaki T, Sato Y, Amano A, Aizawa S, Iwama M, Handa S, Shimada N, Fukuda M, Akita M, Lee J, Jeong KS, Maruyama N, Ishigami A. Vitamin C depletion increases superoxide generation in brains of SMP30/GNL knockout mice. Biochem Biophys Res Commun 2008;377:291–296. doi: 10.1016/j.bbrc.2008.09.132.CrossRefPubMed
14.
go back to reference Sato Y, Kajiyama S, Amano A, Kondo Y, Sasaki T, Handa S, Takahashi R, Fukui M, Hasegawa G, Nakamura N, Fujinawa H, Mori T, Ohta M, Obayashi H, Maruyama N, Ishigami A (2008) Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem Biophys Res Commun 2008;375:346–350. doi: 10.1016/j.bbrc.2008.08.020.CrossRefPubMed Sato Y, Kajiyama S, Amano A, Kondo Y, Sasaki T, Handa S, Takahashi R, Fukui M, Hasegawa G, Nakamura N, Fujinawa H, Mori T, Ohta M, Obayashi H, Maruyama N, Ishigami A (2008) Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem Biophys Res Commun 2008;375:346–350. doi: 10.1016/j.bbrc.2008.08.020.CrossRefPubMed
15.
go back to reference Amano A, Aigaki T, Maruyama N, Ishigami A. Ascorbic acid depletion enhances expression of the sodium-dependent vitamin C transporters, SVCT1 and SVCT2, and uptake of ascorbic acid in livers of SMP30/GNL knockout mice. Arch Biochem Biophys 2010;496:38–44. doi: 10.1016/j.abb.2010.01.012.CrossRefPubMed Amano A, Aigaki T, Maruyama N, Ishigami A. Ascorbic acid depletion enhances expression of the sodium-dependent vitamin C transporters, SVCT1 and SVCT2, and uptake of ascorbic acid in livers of SMP30/GNL knockout mice. Arch Biochem Biophys 2010;496:38–44. doi: 10.1016/j.abb.2010.01.012.CrossRefPubMed
16.
go back to reference Ishikawa Y, Hashizume K, Kishimoto S, Tezuka Y, Nishigori H, Yamamoto N, Kondo Y, Maruyama N, Ishigami A, Kurosaka D. Effect of vitamin C depletion on UVR-B induced cataract in SMP30/GNL knockout mice. Exp Eye Res 2012;94:85–89. doi: 10.1016/j.exer.2011.11.010.CrossRefPubMed Ishikawa Y, Hashizume K, Kishimoto S, Tezuka Y, Nishigori H, Yamamoto N, Kondo Y, Maruyama N, Ishigami A, Kurosaka D. Effect of vitamin C depletion on UVR-B induced cataract in SMP30/GNL knockout mice. Exp Eye Res 2012;94:85–89. doi: 10.1016/j.exer.2011.11.010.CrossRefPubMed
17.
go back to reference Arai KY, Sato Y, Kondo Y, Kudo C, Tsuchiya H, Nomura Y, Ishigami A, Nishiyama T. Effects of vitamin C deficiency on the skin of the senescence marker protein-30 (SMP30) knockout mouse. Biochem Biophys Res Commun 2009;385:478–483. doi: 10.1016/j.bbrc.2009.05.104.CrossRefPubMed Arai KY, Sato Y, Kondo Y, Kudo C, Tsuchiya H, Nomura Y, Ishigami A, Nishiyama T. Effects of vitamin C deficiency on the skin of the senescence marker protein-30 (SMP30) knockout mouse. Biochem Biophys Res Commun 2009;385:478–483. doi: 10.1016/j.bbrc.2009.05.104.CrossRefPubMed
18.
go back to reference Koike K, Kondo Y, Sekiya M, Sato Y, Tobino K, Iwakami SI, Goto S, Takahashi K, Maruyama N, Seyama K, Ishigami A. Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice. Am J Physiol Lung Cell Mol Physiol 2010;298:L784–792. doi: 10.1152/ajplung.00256.2009.CrossRefPubMed Koike K, Kondo Y, Sekiya M, Sato Y, Tobino K, Iwakami SI, Goto S, Takahashi K, Maruyama N, Seyama K, Ishigami A. Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice. Am J Physiol Lung Cell Mol Physiol 2010;298:L784–792. doi: 10.1152/ajplung.00256.2009.CrossRefPubMed
19.
go back to reference Sato Y, Arai KY, Nishiyama T, Nomura Y, Kishimoto Y, Aizawa S, Maruyama N, Ishigami A. Ascorbic acid deficiency leads to epidermal atrophy and UVB-induced skin pigmentation in SMP30/GNL knockout hairless mice. J Invest Dermatol 2012;132:2112–2115. doi: 10.1038/jid.2012.105.CrossRefPubMed Sato Y, Arai KY, Nishiyama T, Nomura Y, Kishimoto Y, Aizawa S, Maruyama N, Ishigami A. Ascorbic acid deficiency leads to epidermal atrophy and UVB-induced skin pigmentation in SMP30/GNL knockout hairless mice. J Invest Dermatol 2012;132:2112–2115. doi: 10.1038/jid.2012.105.CrossRefPubMed
20.
go back to reference Furusawa H, Sato Y, Tanaka Y, Inai Y, Amano A, Iwama M, Kondo Y, Handa S, Murata A, Nishikimi M, Goto S, Maruyama N, Takahashi R, Ishigami A (2008) Vitamin C is not essential for carnitine biosynthesis in vivo: verification in vitamin C-depleted senescence marker protein-30/gluconolactonase knockout mice. Biol Pharm Bull 2008;31:1673–1679.CrossRefPubMed Furusawa H, Sato Y, Tanaka Y, Inai Y, Amano A, Iwama M, Kondo Y, Handa S, Murata A, Nishikimi M, Goto S, Maruyama N, Takahashi R, Ishigami A (2008) Vitamin C is not essential for carnitine biosynthesis in vivo: verification in vitamin C-depleted senescence marker protein-30/gluconolactonase knockout mice. Biol Pharm Bull 2008;31:1673–1679.CrossRefPubMed
21.
go back to reference Iwama M, Shimokado K, Maruyama N, Ishigami A. Time course of vitamin C distribution and absorption after oral administration in SMP30/GNL knockout mice. Nutrition 2011;27:471–478. doi: 10.1016/j.nut.2010.04.010CrossRefPubMed Iwama M, Shimokado K, Maruyama N, Ishigami A. Time course of vitamin C distribution and absorption after oral administration in SMP30/GNL knockout mice. Nutrition 2011;27:471–478. doi: 10.1016/j.nut.2010.04.010CrossRefPubMed
22.
go back to reference Tanaka S, Kuwahara S, Nishijima K, Ohno T, Nagaya M, Nakamura Y, Sumi Y, Miyaishi O, Aoyama H, Goto N. Comparison of rat mandible bone characteristics in F344 substrains, F344/Du and F344/N. Exp Anim 2006 55:415–8.CrossRefPubMed Tanaka S, Kuwahara S, Nishijima K, Ohno T, Nagaya M, Nakamura Y, Sumi Y, Miyaishi O, Aoyama H, Goto N. Comparison of rat mandible bone characteristics in F344 substrains, F344/Du and F344/N. Exp Anim 2006 55:415–8.CrossRefPubMed
23.
go back to reference Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, DC, 2000. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, DC, 2000.
25.
go back to reference Nankivell BJ, Murali KM. Images in clinical medicine. Renal failure from vitamin C after transplantation. N Engl J Med 2008;358:e4. doi: 10.1056/NEJMicm070984.CrossRef Nankivell BJ, Murali KM. Images in clinical medicine. Renal failure from vitamin C after transplantation. N Engl J Med 2008;358:e4. doi: 10.1056/NEJMicm070984.CrossRef
26.
go back to reference Domingo JL, Gomez M, Llobet JM, Jacinto Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney International 1991;39, Issue 4, April 1991, Pages 598–601CrossRefPubMed Domingo JL, Gomez M, Llobet JM, Jacinto Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney International 1991;39, Issue 4, April 1991, Pages 598–601CrossRefPubMed
27.
go back to reference Cannata-Andía JB, Fernández-Martín JL. The clinical impact of aluminium overload in renal failure. Nephrol Dial Transplant. 2002;17 Suppl 2:9–12.CrossRefPubMed Cannata-Andía JB, Fernández-Martín JL. The clinical impact of aluminium overload in renal failure. Nephrol Dial Transplant. 2002;17 Suppl 2:9–12.CrossRefPubMed
28.
go back to reference Cannata-Andía JB, Rodriguez García M, Gómez Alonso C. Osteoporosis and adynamic bone in chronic kidney disease. J Nephrol. 2013 Jan-Feb;26(1):73–80. doi: 10.5301/jn.5000212.CrossRefPubMed Cannata-Andía JB, Rodriguez García M, Gómez Alonso C. Osteoporosis and adynamic bone in chronic kidney disease. J Nephrol. 2013 Jan-Feb;26(1):73–80. doi: 10.5301/jn.5000212.CrossRefPubMed
Metadata
Title
Bone degeneration and its recovery in SMP30/GNL-knockout mice
Authors
Kazutoshi Nishijima
T. Ohno
A. Amano
Y. Kishimoto
Y. Kondo
A. Ishigami
S. Tanaka
Publication date
01-05-2017
Publisher
Springer Paris
Published in
The journal of nutrition, health & aging / Issue 5/2017
Print ISSN: 1279-7707
Electronic ISSN: 1760-4788
DOI
https://doi.org/10.1007/s12603-016-0841-8

Other articles of this Issue 5/2017

The journal of nutrition, health & aging 5/2017 Go to the issue