A-ring analogues of 1, 25-(OH)2D3 with low affinity for the vitamin D receptor modulate chondrocytes via membrane effects that are dependent on cell maturation

Journal of Cellular Physiology
D M GreisingB D Boyan

Abstract

1,25-(OH)2D3 (1,25) and 24,25-(OH)2D3(24,25) mediate their effects on chondrocytes through the classic vitamin D receptor (VDR) as well as through rapid membrane-mediated mechanisms, which result in both nongenomic and genomic effects. In intact cells, it is difficult to distinguish between genomic responses via the VDR and genomic and nongenomic responses via membrane-mediated pathways. In this study, we used two analogues of 1,25 that have been modified on the A-ring (2a, 2b) and are only 0.1% as effective in binding to the VDR as 1,25, to examine the role of the VDR in the response of rat costochondral resting zone (RC) and growth zone (GC) chondrocytes to 1,25 and 24,25. Chondrocyte proliferation ([3H]-thymidine incorporation), proteoglycan production ([35S]-sulfate incorporation), and second messenger activation (activity of protein kinase C) were measured after treatment with 10(-8) M 1,25, 10(-7) M 24,25, or the analogues at 10(-9)-10(-6) M. Both analogues inhibited proliferation of both cell types, as did 1,25 and 24,25. Neither 2a nor 2b had an effect on proteoglycan production by GCs or RCs. 2a caused a dose-dependent stimulation of protein kinase C (PKC) that was not inhibited by cycloheximide or actinomycin D in eit...Continue Reading

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Citations

Sep 17, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·I NemereB D Boyan
Sep 17, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·A W Norman
Jun 3, 1999·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·H A PedrozoB D Boyan
Feb 9, 2000·Frontiers in Neuroendocrinology·B M SchmidtM Wehling
Jul 5, 2002·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·B D BoyanZ Schwartz
Jan 4, 2003·Nature Reviews. Molecular Cell Biology·Ralf Lösel, Martin Wehling
Jan 13, 2006·Journal of Cellular Biochemistry·L N Y WuR E Wuthier
Jul 5, 2003·Physiological Reviews·Ralf M LoselMartin Wehling

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