Regulation of vitamin C transporter in the type 1 diabetic mouse bone and bone marrow

Rajnikumar Sangani, Mohammad Naime, Ibrahim Zakhary, Saif Ahmad, Norman Chutkan, Andy Zhu, Yonju Ha, Mark W Hamrick, Carlos M Isales, Mohammed Elsayed Elsalanty, Sylvia B Smith, Gregory I Liou, Sadanand T Fulzele

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

A number of studies have revealed that Type I diabetes (T1D) is associated with bone loss and an increased risk of fractures. T1D induces oxidative stress in various tissues and organs. Vitamin C plays an important role in the attenuation of oxidative stress; however, little is known about the effect of T1D induced oxidative stress on the regulation of vitamin C transporter in bone and bone marrow cells. To investigate this, T1D was induced in mice by multiple low dose injections of streptozotocin. We have demonstrated that endogenous antioxidants, glutathione peroxidase (GPx) and superoxide dismutase (SOD) are down-regulated in the bone and bone marrow of T1D. The vitamin C transporter isoform SVCT2, the only known transporter expressed in bone and bone marrow stromal cells (BMSCs), is negatively regulated in the bone and bone marrow of T1D. The μCT imaging of the bone showed significantly lower bone quality in the 8. week T1D mouse. The in-vitro study in BMSCS showed that the knockdown of SVCT2 transporter decreases ascorbic acid (AA) uptake, and increases oxidative stress. The significant reversing effect of antioxidant vitamin C is only possible in control cells, not in knockdown cells. This study suggested that T1D induces oxidative stress and decreases SVCT2 expression in the bone and bone marrow environment. Furthermore, this study confirms that T1D increases bone resorption, decreases bone formation and changes the microstructure of bones. This study has provided evidence that the regulation of the SVCT2 transporter plays an important role not only in T1D osteoporosis but also in other oxidative stress-related musculoskeletal complications.

Original languageEnglish (US)
Pages (from-to)298-306
Number of pages9
JournalExperimental and Molecular Pathology
Volume95
Issue number3
DOIs
StatePublished - Jan 1 2013

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Ascorbic Acid
Bone
Bone Marrow
Bone and Bones
Oxidative Stress
Oxidative stress
Antioxidants
Bone Resorption
Streptozocin
Glutathione Peroxidase
Mesenchymal Stromal Cells
Type 1 Diabetes Mellitus
Osteogenesis
Bone Marrow Cells
Osteoporosis
Superoxide Dismutase
Protein Isoforms
Injections
Medical problems
Cells

Keywords

  • Bone marrow stromal cells
  • Type 1 diabetic
  • Vitamin C transporter

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Regulation of vitamin C transporter in the type 1 diabetic mouse bone and bone marrow. / Sangani, Rajnikumar; Naime, Mohammad; Zakhary, Ibrahim; Ahmad, Saif; Chutkan, Norman; Zhu, Andy; Ha, Yonju; Hamrick, Mark W; Isales, Carlos M; Elsalanty, Mohammed Elsayed; Smith, Sylvia B; Liou, Gregory I; Fulzele, Sadanand T.

In: Experimental and Molecular Pathology, Vol. 95, No. 3, 01.01.2013, p. 298-306.

Research output: Contribution to journalArticle

Sangani, Rajnikumar ; Naime, Mohammad ; Zakhary, Ibrahim ; Ahmad, Saif ; Chutkan, Norman ; Zhu, Andy ; Ha, Yonju ; Hamrick, Mark W ; Isales, Carlos M ; Elsalanty, Mohammed Elsayed ; Smith, Sylvia B ; Liou, Gregory I ; Fulzele, Sadanand T. / Regulation of vitamin C transporter in the type 1 diabetic mouse bone and bone marrow. In: Experimental and Molecular Pathology. 2013 ; Vol. 95, No. 3. pp. 298-306.
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AU - Naime, Mohammad

AU - Zakhary, Ibrahim

AU - Ahmad, Saif

AU - Chutkan, Norman

AU - Zhu, Andy

AU - Ha, Yonju

AU - Hamrick, Mark W

AU - Isales, Carlos M

AU - Elsalanty, Mohammed Elsayed

AU - Smith, Sylvia B

AU - Liou, Gregory I

AU - Fulzele, Sadanand T

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N2 - A number of studies have revealed that Type I diabetes (T1D) is associated with bone loss and an increased risk of fractures. T1D induces oxidative stress in various tissues and organs. Vitamin C plays an important role in the attenuation of oxidative stress; however, little is known about the effect of T1D induced oxidative stress on the regulation of vitamin C transporter in bone and bone marrow cells. To investigate this, T1D was induced in mice by multiple low dose injections of streptozotocin. We have demonstrated that endogenous antioxidants, glutathione peroxidase (GPx) and superoxide dismutase (SOD) are down-regulated in the bone and bone marrow of T1D. The vitamin C transporter isoform SVCT2, the only known transporter expressed in bone and bone marrow stromal cells (BMSCs), is negatively regulated in the bone and bone marrow of T1D. The μCT imaging of the bone showed significantly lower bone quality in the 8. week T1D mouse. The in-vitro study in BMSCS showed that the knockdown of SVCT2 transporter decreases ascorbic acid (AA) uptake, and increases oxidative stress. The significant reversing effect of antioxidant vitamin C is only possible in control cells, not in knockdown cells. This study suggested that T1D induces oxidative stress and decreases SVCT2 expression in the bone and bone marrow environment. Furthermore, this study confirms that T1D increases bone resorption, decreases bone formation and changes the microstructure of bones. This study has provided evidence that the regulation of the SVCT2 transporter plays an important role not only in T1D osteoporosis but also in other oxidative stress-related musculoskeletal complications.

AB - A number of studies have revealed that Type I diabetes (T1D) is associated with bone loss and an increased risk of fractures. T1D induces oxidative stress in various tissues and organs. Vitamin C plays an important role in the attenuation of oxidative stress; however, little is known about the effect of T1D induced oxidative stress on the regulation of vitamin C transporter in bone and bone marrow cells. To investigate this, T1D was induced in mice by multiple low dose injections of streptozotocin. We have demonstrated that endogenous antioxidants, glutathione peroxidase (GPx) and superoxide dismutase (SOD) are down-regulated in the bone and bone marrow of T1D. The vitamin C transporter isoform SVCT2, the only known transporter expressed in bone and bone marrow stromal cells (BMSCs), is negatively regulated in the bone and bone marrow of T1D. The μCT imaging of the bone showed significantly lower bone quality in the 8. week T1D mouse. The in-vitro study in BMSCS showed that the knockdown of SVCT2 transporter decreases ascorbic acid (AA) uptake, and increases oxidative stress. The significant reversing effect of antioxidant vitamin C is only possible in control cells, not in knockdown cells. This study suggested that T1D induces oxidative stress and decreases SVCT2 expression in the bone and bone marrow environment. Furthermore, this study confirms that T1D increases bone resorption, decreases bone formation and changes the microstructure of bones. This study has provided evidence that the regulation of the SVCT2 transporter plays an important role not only in T1D osteoporosis but also in other oxidative stress-related musculoskeletal complications.

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