Glucocorticoid stimulation of Na+-dependent ascorbic acid transport in osteoblast-like cells

Department of Periodontics, Prevention, and Geriatrics, School of Dentistry, University of Michigan, Ann Arbor 48109-1078, USA.
Journal of Cellular Physiology (Impact Factor: 3.84). 07/1998; 176(1):85-91. DOI: 10.1002/(SICI)1097-4652(199807)176:1<85::AID-JCP10>3.0.CO;2-N
Source: PubMed


Ascorbic acid (AA) is an essential cofactor for osteoblast differentiation both in vivo and in vitro. Before it can function, this vitamin must be transported into cells via a specific Na+-dependent AA transporter. In this study, we examine the regulation of this transport activity by glucocorticoids, a class of steroid hormones known to stimulate in vitro osteoblast differentiation. Dexamethasone stimulated Na+-dependent AA transport activity approximately twofold in primary rat calvarial osteoblasts. Effects of hormone on ascorbic acid transport were rapid (detected within 24 h) and were maximally stimulated by 25-50 nM dexamethasone. Similar effects of dexamethasone on transport activity were also observed in murine MC3T3-E1 cells. This preosteoblast cell line was used for a more detailed characterization of the glucocorticoid response. Transport activity was stimulated selectively by glucocorticoids (dexamethasone > corticosterone) relative to other steroid hormones (progesterone and 17-beta-estradiol) and was blocked when cells were cultured in the presence of cycloheximide, a protein synthesis inhibitor. Kinetic analysis of AA transporter activity in control and dexamethasone-treated cells indicated a Km of approximately 17 microM for both groups. In contrast, dexamethasone increased Vmax by approximately 2.5-fold. Cells also contained an Na+-independent glucose transport activity that has been reported in other systems to transport vitamin C as oxidized dehydroascorbic acid. In marked contrast to Na+-dependent AA transport, this activity was inhibited by dexamethasone. Thus, glucocorticoids increase Na+-dependent AA transport in osteoblasts, possibly via up-regulation of transporter synthesis, and this response can be resolved from actions of glucocorticoids on glucose transport.

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    • "Several factors such as hormones and growth factors also affect osteoblastic cell function. For example, Dex or transforming growth factor b can stimulate not only the synthesis of extracellular matrix but also Na + -dependant l-[ 14 C]AsA uptake (Wilson & Dixon, 1995; Pandipati et al. 1998). However, the relationship between these actions and the expression of AsA transporters was unknown. "
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    ABSTRACT: The regulation of intracellular ascorbic acid (AsA) levels may be under the control of an AsA-specific membrane transporter. The present study investigates AsA uptake and expression of Na-dependent vitamin C transporter (SVCT) mRNA in the mouse osteoblastic cell line, MC3T3-E1. Among eight compounds tested, dexamethasone (Dex) all-trans retinoic acid, transforming growth factor beta, prostaglandin E2 and transferrin significantly and respectively) stimulated the update of AsA into MC3T3-E1 cells. Among these five, Dex was the most active, inducing mSVCT2 mRNA and the uptake of AsA in a time- and concentration-dependant manner. Dex did not induce mSVCT1 mRNA. These results suggest that the Dex-induced stimulation of AsA incorporation into osteoblastic cells is mediated by the induction of mSVCT2. Since Dex reduced alkaline phosphatase activity in MC3T3-E1 cells in our culture conditions, Dex-induced stimulation of AsA incorporation might not be the result of differentiation. Hormone-regulated changes of SVCT expression may have an important role in cell functions.
    Full-text · Article · Sep 2001 · British Journal Of Nutrition

  • No preview · Article · Sep 1999 · Journal of Intensive Care Medicine
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    No preview · Article · Oct 1999 · Journal of Intensive Care Medicine
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