Document Detail

Sodium-dependent vitamin C transporter SVCT2: expression and function in bone marrow stromal cells and in osteogenesis.
MedLine Citation:
PMID:  23089627     Owner:  NLM     Status:  MEDLINE    
Ascorbic acid (Vitamin C) has a critical role in bone formation and osteoblast differentiation, but very little is known about the molecular mechanisms of ascorbic acid entry into bone marrow stromal cells (BMSCs). To address this gap in knowledge, we investigated the identity of the transport system that is responsible for the uptake of ascorbic acid into bone marrow stromal cells (BMSCs). First, we examined the expression of the two known isoforms of the sodium-coupled ascorbic acid transporter, namely SVCT1 and SVCT2, in BMSCs (Lin-ve Sca1+ve) and bone at the mRNA level. Only SVCT2 mRNA was detected in BMSCs and bone. Uptake of ascorbic acid in BMSCs was Na(+)-dependent and saturable. In order to define the role of SVCT2 in BMSC differentiation into osteoblasts, BMSCs were stimulated with osteogenic media for different time intervals, and the activity of SVCT2 was monitored by ascorbic acid uptake. SVCT2 expression was up-regulated during the osteogenic differentiation of BMSCs; the expression was maximal at the earliest phase of differentiation. Subsequently, osteogenesis was inhibited in BMSCs upon knock-down of SVCT2 by lentivirus shRNA. We also found that the expression of the SVCT2 could be negatively or positively modulated by the presence of oxidant (Sin-1) or antioxidant (Ascorbic acid) compounds, respectively, in BMSCs. Furthermore, we found that this transporter is also regulated with age in mouse bone. These data show that SVCT2 plays a vital role in the osteogenic differentiation of BMSCs and that its expression is altered under conditions associated with redox reaction. Our findings could be relevant to bone tissue engineering and bone related diseases such as osteoporosis in which oxidative stress and aging plays important role.
Sadanand Fulzele; Paresh Chothe; Rajnikumar Sangani; Norman Chutkan; Mark Hamrick; Maryka Bhattacharyya; Puttur D Prasad; Ibrahim Zakhary; Matthew Bowser; Carlos Isales; Vadivel Ganapathy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-23
Journal Detail:
Title:  Stem cell research     Volume:  10     ISSN:  1876-7753     ISO Abbreviation:  Stem Cell Res     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-18     Completed Date:  2013-05-31     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  101316957     Medline TA:  Stem Cell Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  36-47     Citation Subset:  IM    
Copyright Information:
Published by Elsevier B.V.
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MeSH Terms
Antioxidants / pharmacology
Ascorbic Acid / pharmacology
Bone and Bones / metabolism
Cell Differentiation / drug effects
Cells, Cultured
Mesenchymal Stromal Cells / cytology,  metabolism*
Mice, Inbred C57BL
Osteogenesis / drug effects
Protein Isoforms / genetics,  metabolism
RNA Interference
RNA, Small Interfering / metabolism
Skull / metabolism
Sodium / metabolism
Sodium-Coupled Vitamin C Transporters / antagonists & inhibitors,  genetics,  metabolism*
Time Factors
Tissue Engineering
Up-Regulation / drug effects
Grant Support
Reg. No./Substance:
0/Antioxidants; 0/Protein Isoforms; 0/RNA, Small Interfering; 0/Sodium-Coupled Vitamin C Transporters; 9NEZ333N27/Sodium; PQ6CK8PD0R/Ascorbic Acid

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