title: Regulation of vitamin C transporter in the type 1 diabetic mouse bone and bone marrow.
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.
authors.affiliation: Departments of Orthopaedic Surgery, Georgia Regents University, Augusta, GA 30912, United States.
authors.forename: Rajnikumar
authors.initials: R
authors.lastname: Sangani
authors.forename: Mohammad
authors.initials: M
authors.lastname: Naime
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Zakhary
authors.forename: Saif
authors.initials: S
authors.lastname: Ahmad
authors.forename: Norman
authors.initials: N
authors.lastname: Chutkan
authors.forename: Andy
authors.initials: A
authors.lastname: Zhu
authors.forename: Yonju
authors.initials: Y
authors.lastname: Ha
authors.forename: Mark
authors.initials: M
authors.lastname: Hamrick
authors.forename: Carlos
authors.initials: C
authors.lastname: Isales
authors.forename: Mohammed
authors.initials: M
authors.lastname: Elsalanty
authors.forename: Sylvia
authors.initials: S
authors.lastname: Smith
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Liou
authors.forename: Sadanand
authors.initials: S
authors.lastname: Fulzele
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060347:Sodium-Coupled Vitamin C Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D060347:Sodium-Coupled Vitamin C Transporters; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Bone marrow stromal cells; Type 1 diabetic; Vitamin C transporter