Zinc-induced sodium-dependent vitamin C transporter 2 expression: potent roles in osteoblast differentiation.
Zinc is an essential trace element that increases osteoblast numbers and bone formation. However, the mechanisms involved in the Zn-induced differentiation of osteoblasts are poorly understood. We examined the roles of L-ascorbic acid (AA) and its transporter, sodium-dependent vitamin C transporter (SVCT) 2, in the Zn-induced expression of osteoblastic differentiation markers. Zinc time- and dose-dependently induced SVCT2 mRNA expression in the absence or presence of AA. Western blotting and kinetic assays showed that Zn increased functional SVCT2 protein levels and AA transport. In the presence of AA, 50 microM Zn enhanced mRNA expression of the osteoblastic differentiation markers alkaline phosphatase, alpha(1)(I) procollagen, osteopontin (OPN), and osteocalcin (OCN) by 3.9-, 3.8-, 3.3-, and 3.5-fold, respectively; in the absence of AA, the Zn-induced increase was 2.8-, 2.5-, 1.3-, and 1.1-fold, respectively. These findings suggest that AA and SVCT2 mediate Zn-induced OPN and OCN expression and partly regulate Zn-induced osteoblastic differentiation.
Wu
Ximei
X
Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Itoh
Norio
N
Taniguchi
Takashi
T
Nakanishi
Tsuyoshi
T
Tatsu
Yoshiro
Y
Yumoto
Noboru
N
Tanaka
Keiichi
K
D016475:3T3 Cells; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D051379:Mice; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*
D029363:Organic Anion Transporters, Sodium-Dependent; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D015032:Zinc; D001205:Ascorbic Acid