Abstract
We examined the ability of 1,25 (OH)(2) vitamin D(3) (Vit D) to stimulate osteoclast-like cell (OCL) formation in cocultures of spleen cells and primary calvarial osteoblasts from wild-type (WT) and IL-1R type 1-deficient (knockout; KO) mice. Vit D dose dependently increased OCL in cocultures containing WT osteoblasts. In contrast, there was a 90% reduction in OCL numbers in cocultures containing KO osteoblasts. In cocultures with either WT or KO osteoblasts, treatment with Vit D increased receptor activator of NF-kappaB ligand mRNA by 17-, 19-, or 3.5-fold, respectively. Vit D decreased osteoprotegerin mRNA to undetectable in all groups. Intracellular IL-1alpha protein increased after Vit D treatment in cocultures containing WT, but not KO osteoblasts. We also examined direct effects of Vit D, IL-1alpha, and their combination on gene expression in primary osteoblasts. In WT cells, Vit D and IL-1 stimulated receptor activator of NF-kappaB ligand mRNA expression by 3- and 4-fold, respectively, and their combination produced a 7-fold increase. Inhibition of osteoprotegerin mRNA in WT cells was partial with either agent alone and greatest with their combination. In KO cells, only Vit D stimulated a response. IL-1 alone increased IL-1alpha protein expression in WT osteoblasts. However, in combination with Vit D, there was a synergistic response (100-fold increase). In KO cultures, there were no effects of IL-1, Vit D, or their combination on IL-1alpha protein. These results demonstrate interactions between IL-1 and Vit D in primary osteoblasts that appear important in both regulation of IL-1alpha production and the ability of Vit D to support osteoclastogenesis.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / biosynthesis
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Adjuvants, Immunologic / physiology
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Animals
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Calcitriol / antagonists & inhibitors
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Calcitriol / pharmacology*
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Carrier Proteins / biosynthesis*
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Carrier Proteins / genetics
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Carrier Proteins / physiology
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Cells, Cultured
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Coculture Techniques
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Glycoproteins / antagonists & inhibitors
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Glycoproteins / genetics
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Glycoproteins / metabolism*
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1 / antagonists & inhibitors
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Interleukin-1 / biosynthesis*
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Interleukin-1 / genetics
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Interleukin-1 / physiology
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Ligands
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Male
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NF-kappa B / metabolism
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Osteoblasts / drug effects
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Osteoblasts / metabolism*
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Osteoblasts / physiology
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Osteoclasts / cytology*
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Osteoclasts / drug effects
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Osteoclasts / physiology
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Osteogenesis / drug effects*
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Osteogenesis / immunology
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Osteoprotegerin
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RANK Ligand
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RNA, Messenger / biosynthesis
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Tumor Necrosis Factor
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Sialoglycoproteins / pharmacology
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Spleen / cytology*
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Spleen / drug effects
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Spleen / physiology
Substances
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Adjuvants, Immunologic
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Carrier Proteins
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Glycoproteins
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Il1rn protein, mouse
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1
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Ligands
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Membrane Glycoproteins
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NF-kappa B
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Osteoprotegerin
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RANK Ligand
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RNA, Messenger
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Cytoplasmic and Nuclear
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Receptors, Tumor Necrosis Factor
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Sialoglycoproteins
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Tnfrsf11a protein, mouse
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Tnfrsf11b protein, mouse
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Tnfsf11 protein, mouse
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Calcitriol