Bile acids and bilirubin effects on osteoblastic gene profile. Implications in the pathogenesis of osteoporosis in liver diseases
| Autor: | Núria Guañabens, Silvia Ruiz-Gaspà, Albert Parés, Pilar Peris, Andrés Combalia, Susana Jurado, Marta Dubreuil, Ana Monegal |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Lithocholic acid Down-Regulation Apoptosis Bile Acids and Salts 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Internal medicine Matrix gla protein Genetics medicine Humans Osteopontin Calcitonin receptor Osteosarcoma Cholestasis Osteoblasts biology Liver Diseases Ursodeoxycholic Acid Bilirubin General Medicine Genetic Profile Ursodeoxycholic acid Up-Regulation Bone morphogenetic protein 7 030104 developmental biology Endocrinology Liver chemistry 030220 oncology & carcinogenesis biology.protein Osteocalcin Osteoporosis Lithocholic Acid Osteonectin medicine.drug |
| Popis: | Osteoporosis in advanced cholestatic and end-stage liver disease is related to low bone formation. Previous studies have demonstrated the deleterious consequences of lithocholic acid (LCA) and bilirubin on osteoblastic cells. These effects are partially or completely neutralized by ursodeoxycholic acid (UDCA). We have assessed the differential gene expression of osteoblastic cells under different culture conditions. The experiments were performed in human osteosarcoma cells (Saos-2) cultured with LCA 10 μM), bilirubin (50 μM) or UDCA (10 and 100 μM) at 2 and 24 hours. Expression of 87 genes related to bone metabolism and other signalling pathways were assessed by TaqMan micro fluidic cards. Several genes were up-regulated by LCA, most of them pro-apoptotic (BAX,BCL10,BCL2L13,BCL2L14), but alsoMGP(matrix Gla protein), BGLAP(osteocalcin),SPP1(osteopontin) andCYP24A1, and down-regulated bone morphogenic protein genes (BMP3andBMP4) andDKK1(Dickkopf-related protein 1). Parallel effects were observed with bilirubin, which up-regulated apoptotic genes andCSF2(colony-stimulating factor 2) and down-regulated antiapoptotic genes (BCL2andBCL2L1),BMP3,BMP4and RUNX2. UDCA 100 μM had specific consequences since differential expression was observed, up-regulatingBMP2,BMP4,BMP7,CALCR(calcitonin receptor),SPOCK3(osteonectin),BGLAP(osteocalcin) andSPP1(osteopontin), and down-regulating pro-apoptotic genes. Furthermore, most of the differential expression changes induced by both LCA and bilirubin were partially or completely neutralized by UDCA.Conclusion: Our observations reveal novel target genes, whose regulation by retained substances of cholestasis may provide additional insights into the pathogenesis of osteoporosis in cholestatic and end-stage liver diseases. |
| Databáze: | OpenAIRE |
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