Hydrocortisone and deflazacort induce different effects on vitamin D receptor level increase produced by 1,25-dihydroxyvitamin D3 in rat osteoblast-like UMR-106 cells. 2004

Rosa Guerrero, and Concepción de la Piedra, and Emma Teixeiro, and Rafael Bragado, and Maria Luisa Traba
Biochemistry Laboratory, Bone Pathophysiology Section, and Immunology Section, Fundación Jiménez Díaz, Madrid, Spain.

OBJECTIVE The homologous upregulation produced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on vitamin D receptor (VDR) levels, and the effects produced by the heterologous agents hydrocortisone or deflazacort, alone or in conjunction with this vitamin D metabolite, were studied in rat osteoblastic UMR-106 osteosarcoma cells. METHODS VDR were determined by binding analysis (Bmax and dissociation constant). VDR mRNA expression levels were measured by Northern blot analysis. RESULTS Incubation with 10 nM 1,25(OH)2D3 produced a significant increase in Bmax with respect to ethanol-treated cells (100.2 +/- 13.2 vs 11.4 +/- 4.8 fmol 3H-1,25(OH)2D3 bound/mg protein) together with a significant increase in VDR mRNA expression (483 +/- 170% vs 100%). The addition of 10 nM hydrocortisone to 1,25(OH)2D3 produced a significant decrease in Bmax (from 100.2 +/- 13.2 to 44 +/- 5.6), with mRNA levels similar to those of basal conditions (116 +/- 25% vs 100%). However, the addition of 10 nM deflazacort did not reduce the activation in Bmax produced by 1,25(OH)2D3 (92.4 +/- 16 vs 100.2 +/- 13.2), maintaining the increase in mRNA levels (430 +/- 10% vs 483 +/- 170%). If 10 nM hydrocortisone or 10 nM deflazacort was added to UMR-106 cells without 1,25(OH)2D3, a similar increase was observed in Bmax with respect to basal conditions (20.4 +/- 1.3 or 20.9 +/- 1.6 vs 11.4 +/- 4.8 in control cells), but hydrocortisone did not produce any significant variation in mRNA VDR levels, while deflazacort itself produced an increase in VDR mRNA expression. CONCLUSIONS Our findings of different actions produced by hydrocortisone and deflazacort on the increase of VDR levels produced by 1,25(OH)2D3 could explain some of the different actions produced by both antiinflammatory medications on bone metabolism.

UI MeSH Term Description Entries
D010006 Osteoblasts Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone. Osteoblast
D011282 Pregnenediones Unsaturated pregnane derivatives containing two keto groups on side chains or ring structures. Diketopregnenes,Dioxopregnenes
D002117 Calcitriol The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. 1 alpha,25-Dihydroxycholecalciferol,1 alpha,25-Dihydroxyvitamin D3,1, 25-(OH)2D3,1,25(OH)2D3,1,25-Dihydroxycholecalciferol,1,25-Dihydroxyvitamin D3,1 alpha, 25-dihydroxy-20-epi-Vitamin D3,1,25(OH)2-20epi-D3,1,25-dihydroxy-20-epi-Vitamin D3,20-epi-1alpha,25-dihydroxycholecaliferol,Bocatriol,Calcijex,Calcitriol KyraMed,Calcitriol-Nefro,Decostriol,MC-1288,MC1288,Osteotriol,Renatriol,Rocaltrol,Silkis,Sitriol,Soltriol,Tirocal,1 alpha,25 Dihydroxyvitamin D3,1,25 Dihydroxycholecalciferol,1,25 Dihydroxyvitamin D3,1,25 dihydroxy 20 epi Vitamin D3,Calcitriol Nefro,D3, 1 alpha,25-Dihydroxyvitamin,D3, 1,25-Dihydroxyvitamin,D3, 1,25-dihydroxy-20-epi-Vitamin,KyraMed, Calcitriol,MC 1288
D002120 Calcium Channel Agonists Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture. Calcium Channel Activators,Calcium Channel Agonists, Exogenous,Calcium Channel Agonist,Exogenous Calcium Channel Agonists,Activators, Calcium Channel,Agonist, Calcium Channel,Agonists, Calcium Channel,Channel Activators, Calcium,Channel Agonist, Calcium,Channel Agonists, Calcium
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006854 Hydrocortisone The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000893 Anti-Inflammatory Agents Substances that reduce or suppress INFLAMMATION. Anti-Inflammatory Agent,Antiinflammatory Agent,Agents, Anti-Inflammatory,Agents, Antiinflammatory,Anti-Inflammatories,Antiinflammatories,Antiinflammatory Agents,Agent, Anti-Inflammatory,Agent, Antiinflammatory,Agents, Anti Inflammatory,Anti Inflammatories,Anti Inflammatory Agent,Anti Inflammatory Agents
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014316 Tritium The radioactive isotope of hydrogen also known as hydrogen-3. It contains two NEUTRONS and one PROTON in its nucleus and decays to produce low energy BETA PARTICLES. Hydrogen-3,Hydrogen 3

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