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Published in: BMC Musculoskeletal Disorders 1/2014

Open Access 01-12-2014 | Research article

Comparative analysis of sodium coupled vitamin C transporter 2 in human osteoarthritis grade 1 and grade 3 tissues

Authors: Alan R Blackburn II, Mark W Hamrick, Norman Chutkan, Rajnikumar Sangani, Jennifer L Waller, Raymond Corpe, Puttur D Prasad, Carlos M Isales, Vadivel Ganapathy, Sadanand Fulzele

Published in: BMC Musculoskeletal Disorders | Issue 1/2014

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Abstract

Background

Nutrient levels are known to influence the development of osteoarthritis (OA), presumably by modulating levels of matrix biosynthesis and degradation. These processes may be affected by ascorbic acid (AA), an antioxidant which acts as a cofactor for numerous biochemical reactions and is essential for post-translational modifications of collagen. In this study we examined the expression of SVCT2, the only known Sodium coupled vitamin C transporter isoform present in articular cartilage, in human articular cartilage explants derived from both normal and osteoarthritis articular cartilage.

Methods

OA1 and OA3 human articular cartilage was carefully dissected and macroscopically graded for degeneration via the Collins scale. The tissue samples were histologically examined by Hematoxylin and Eosin and Safranin O and Fast Green staining. SVCT2 expression analysis was performed at mRNA level by quantitative real time PCR and at a protein level by immunohistochemistry.

Results

Our quantitative real time PCR showed marked variation in the expression of SVCT2 in human osteoarthritic articular cartilage. SVCT2 expression was significantly down-regulated (p = 0.0001) in the Collins grade 3 (OA3) compared to Collins grade 1 (OA1) tissue. Furthermore, slides stained with fluorescent antibodies to SVCT2 demonstrated greatly reduced fluorescence for the SVCT2 transporter on the chondrocyte plasma membrane in the osteoarthritic tissue samples.

Conclusions

These findings demonstrate that the expression of SVCT2 transporter is significantly altered in human osteoarthritic tissues (OA3). The modulation of this transporter could therefore potentially influence the prevention, management and treatment of osteoarthritis.
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Literature
1.
go back to reference Gabay O, Hall DJ, Berenbaum F, Henrotin Y, Sanchez C: Osteoarthritis and obesity: experimental models. Joint Bone Spine. 2008, 75 (6): 675-679. 10.1016/j.jbspin.2008.07.011. Epub 2008 Nov 20CrossRefPubMedPubMedCentral Gabay O, Hall DJ, Berenbaum F, Henrotin Y, Sanchez C: Osteoarthritis and obesity: experimental models. Joint Bone Spine. 2008, 75 (6): 675-679. 10.1016/j.jbspin.2008.07.011. Epub 2008 Nov 20CrossRefPubMedPubMedCentral
2.
go back to reference Altindag O, Erel O, Aksoy N, Selek S, Celik H, Karaoglanoglu M: Increased oxidative stress and its relation with collagen metabolism in knee osteoarthritis. Rheumatol Int. 2007, 27 (4): 339-344. 10.1007/s00296-006-0247-8.CrossRefPubMed Altindag O, Erel O, Aksoy N, Selek S, Celik H, Karaoglanoglu M: Increased oxidative stress and its relation with collagen metabolism in knee osteoarthritis. Rheumatol Int. 2007, 27 (4): 339-344. 10.1007/s00296-006-0247-8.CrossRefPubMed
3.
go back to reference Wang Y, Prentice LF, Vitetta L, Wluka AE, Cicuttini FM: The effect of nutritional supplements on osteoarthritis. Altern Med Rev. 2004, 9 (3): 275-296. ReviewPubMed Wang Y, Prentice LF, Vitetta L, Wluka AE, Cicuttini FM: The effect of nutritional supplements on osteoarthritis. Altern Med Rev. 2004, 9 (3): 275-296. ReviewPubMed
4.
go back to reference Levine M, Rumsey SC, Daruwala RC, Park JB, Wang Y: Criteria and recommendations for vitamin C intake. JAMA. 1999, 281: 1415-1423. 10.1001/jama.281.15.1415.CrossRefPubMed Levine M, Rumsey SC, Daruwala RC, Park JB, Wang Y: Criteria and recommendations for vitamin C intake. JAMA. 1999, 281: 1415-1423. 10.1001/jama.281.15.1415.CrossRefPubMed
5.
go back to reference Garvican ER, Vaughan-Thomas A, Innes JF, Clegg PD: Biomarkers of cartilage turnover. Part 1: markers of collagen degradation and synthesis. Vet J. 2010, 185 (1): 36-42. 10.1016/j.tvjl.2010.04.011.CrossRefPubMed Garvican ER, Vaughan-Thomas A, Innes JF, Clegg PD: Biomarkers of cartilage turnover. Part 1: markers of collagen degradation and synthesis. Vet J. 2010, 185 (1): 36-42. 10.1016/j.tvjl.2010.04.011.CrossRefPubMed
6.
go back to reference Clark AG, Rohrbaugh AL, Otterness I, Kraus VB: The effects of ascorbic acid on cartilage metabolism in guinea pig articular cartilage explants. Matrix Biol. 2002, 21: 175-184. 10.1016/S0945-053X(01)00193-7.CrossRefPubMed Clark AG, Rohrbaugh AL, Otterness I, Kraus VB: The effects of ascorbic acid on cartilage metabolism in guinea pig articular cartilage explants. Matrix Biol. 2002, 21: 175-184. 10.1016/S0945-053X(01)00193-7.CrossRefPubMed
7.
go back to reference McNulty AL, Vail TP, Kraus VB: Chondrocyte transport and concentration of ascorbic acid is mediated by SVCT2. Biochim Biophys Acta. 2005, 1712 (2): 212-221. 10.1016/j.bbamem.2005.04.009.CrossRefPubMed McNulty AL, Vail TP, Kraus VB: Chondrocyte transport and concentration of ascorbic acid is mediated by SVCT2. Biochim Biophys Acta. 2005, 1712 (2): 212-221. 10.1016/j.bbamem.2005.04.009.CrossRefPubMed
8.
go back to reference Collins DH: The Pathology of Articular and Spinal Diseases. 1949, London: Edward Arnold Co. Collins DH: The Pathology of Articular and Spinal Diseases. 1949, London: Edward Arnold Co.
9.
go back to reference Wu X, Iguchi T, Itoh N, Okamoto K, Takagi T, Tanaka K: Ascorbic acid transported by sodium-dependent vitamin C transporter 2 stimulates steroidogenesis in human choriocarcinoma cells. Endocrinology. 2008, 149 (1): 73-83. 10.1210/en.2007-0262.CrossRefPubMed Wu X, Iguchi T, Itoh N, Okamoto K, Takagi T, Tanaka K: Ascorbic acid transported by sodium-dependent vitamin C transporter 2 stimulates steroidogenesis in human choriocarcinoma cells. Endocrinology. 2008, 149 (1): 73-83. 10.1210/en.2007-0262.CrossRefPubMed
10.
go back to reference Schwartz ER, Oh W, Leveille C: Experimentally induced osteoarthritis in guinea pigs. Arthritis Rheum. 1981, 24: 1345-1355. 10.1002/art.1780241103.CrossRefPubMed Schwartz ER, Oh W, Leveille C: Experimentally induced osteoarthritis in guinea pigs. Arthritis Rheum. 1981, 24: 1345-1355. 10.1002/art.1780241103.CrossRefPubMed
11.
go back to reference McAlindon TE, Jacques P, Zhang Y, Hannan MT, Aliabadi P, Weissman B: Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis?. Arthritis Rheum. 1996, 39 (4): 648-656. 10.1002/art.1780390417.CrossRefPubMed McAlindon TE, Jacques P, Zhang Y, Hannan MT, Aliabadi P, Weissman B: Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis?. Arthritis Rheum. 1996, 39 (4): 648-656. 10.1002/art.1780390417.CrossRefPubMed
12.
go back to reference Tsukaguchi H, Tokui T, Mackenzie B, Berger UV, Chen XZ, Wang Y: A family of mammalian Na + −dependent L-ascorbic acid transporters. Nature. 1999, 399: 70-75. 10.1038/19986.CrossRefPubMed Tsukaguchi H, Tokui T, Mackenzie B, Berger UV, Chen XZ, Wang Y: A family of mammalian Na + −dependent L-ascorbic acid transporters. Nature. 1999, 399: 70-75. 10.1038/19986.CrossRefPubMed
13.
go back to reference Michels AJ, Joisher N, Hagen TM: Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes. Arch Biochem Biophys. 2003, 410: 112-120. 10.1016/S0003-9861(02)00678-1.CrossRefPubMed Michels AJ, Joisher N, Hagen TM: Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes. Arch Biochem Biophys. 2003, 410: 112-120. 10.1016/S0003-9861(02)00678-1.CrossRefPubMed
14.
go back to reference Savini I, Rossi A, Pierro C, Avigliano L, Catani MV: SVCT1 and SVCT2: key proteins for vitamin C uptake. Amino Acids. 2008, 34 (3): 347-355. 10.1007/s00726-007-0555-7. Epub 2007 Jun 1. ReviewCrossRefPubMed Savini I, Rossi A, Pierro C, Avigliano L, Catani MV: SVCT1 and SVCT2: key proteins for vitamin C uptake. Amino Acids. 2008, 34 (3): 347-355. 10.1007/s00726-007-0555-7. Epub 2007 Jun 1. ReviewCrossRefPubMed
15.
go back to reference Seno T, Inoue N, Matsui K, Ejiri J, Hirata K, Kawashima S: Functional expression of sodium-dependent vitamin C transporter 2 in human endothelial cells. J Vasc Res. 2004, 41 (4): 345-351. 10.1159/000080525.CrossRefPubMed Seno T, Inoue N, Matsui K, Ejiri J, Hirata K, Kawashima S: Functional expression of sodium-dependent vitamin C transporter 2 in human endothelial cells. J Vasc Res. 2004, 41 (4): 345-351. 10.1159/000080525.CrossRefPubMed
16.
go back to reference Kannan R, Stolz A, Ji Q, Prasad PD, Ganapathy V: Vitamin C transport in human lens epithelial cells: evidence for the presence of SVCT-2. Exp Eye Res. 2001, 73: 159-165. 10.1006/exer.2001.1024.CrossRefPubMed Kannan R, Stolz A, Ji Q, Prasad PD, Ganapathy V: Vitamin C transport in human lens epithelial cells: evidence for the presence of SVCT-2. Exp Eye Res. 2001, 73: 159-165. 10.1006/exer.2001.1024.CrossRefPubMed
17.
go back to reference Savini I, Rossi A, Catani MV, Ceci R, Avigliano L: Redox regulation of vitamin C transporter SVCT2 in C2C12 myotubes. Biochem Biophys Res Commun. 2007, 361 (2): 385-390. 10.1016/j.bbrc.2007.07.007.CrossRefPubMed Savini I, Rossi A, Catani MV, Ceci R, Avigliano L: Redox regulation of vitamin C transporter SVCT2 in C2C12 myotubes. Biochem Biophys Res Commun. 2007, 361 (2): 385-390. 10.1016/j.bbrc.2007.07.007.CrossRefPubMed
18.
go back to reference Fulzele S, Chothe P, Sangani R, Chutkan N, Hamrick M, Bhattacharyya M, Prasad PD, Zakhary I, Bowser M, Isales C, Ganapathy V: Sodium-dependent vitamin C transporter SVCT2: expression and function in bone marrow stromal cells and in osteogenesis. Stem Cell Res. 2013, 10 (1): 36-47. 10.1016/j.scr.2012.08.004.CrossRefPubMed Fulzele S, Chothe P, Sangani R, Chutkan N, Hamrick M, Bhattacharyya M, Prasad PD, Zakhary I, Bowser M, Isales C, Ganapathy V: Sodium-dependent vitamin C transporter SVCT2: expression and function in bone marrow stromal cells and in osteogenesis. Stem Cell Res. 2013, 10 (1): 36-47. 10.1016/j.scr.2012.08.004.CrossRefPubMed
Metadata
Title
Comparative analysis of sodium coupled vitamin C transporter 2 in human osteoarthritis grade 1 and grade 3 tissues
Authors
Alan R Blackburn II
Mark W Hamrick
Norman Chutkan
Rajnikumar Sangani
Jennifer L Waller
Raymond Corpe
Puttur D Prasad
Carlos M Isales
Vadivel Ganapathy
Sadanand Fulzele
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2014
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-15-9

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