Effect of rapamycin on hepatic osteodystrophy in rats with portasystemic shunting
| Autor: | Enid G. Shephard, Robert P. Bond, Martin Nieuwoudt, Elongo Lekunze Fritz, Brenda J. Olivier, D Kahn, G. H. C. Engelbrecht, Stephen Hough, Schalk Van der Merwe, Rhena Delport, Nico J. P. de Villiers, M M Conradie, Tomas Slavik, Maritha J. Kotze |
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| Přispěvatelé: | Tytgat Institute for Liver and Intestinal Research |
| Předmět: |
musculoskeletal diseases
Male medicine.medical_specialty medicine.medical_treatment Osteoclasts CD8-Positive T-Lymphocytes Lymphocyte Activation Body Mass Index Bone remodeling Rats Sprague-Dawley Eating Liver disease Bone Density Internal medicine medicine Animals Portasystemic Shunt Surgical Bone Resorption Sirolimus Membrane Glycoproteins Tumor Necrosis Factor-alpha business.industry RANK Ligand Gastroenterology Histology General Medicine medicine.disease Rats Osteopenia Shunting Hepatic osteodystrophy Basic Research Cytokine Endocrinology Gene Expression Regulation Cytokines Osteoporosis medicine.symptom Carrier Proteins business Weight gain Immunosuppressive Agents |
| Zdroj: | Scopus-Elsevier World journal of gastroenterology, 12(28), 4504-4510. WJG Press |
| ISSN: | 1007-9327 |
| Popis: | To study if T-cell activation related to portasystemic shunting causes osteoclast-mediated bone loss through RANKL-dependent pathways. We also investigated if T-cell inhibition using rapamycin would protect against bone loss in rats. Portasystemic shunting was performed in male Sprague-Dawley rats and rapamycin 0.1 mg/kg was administered for 15 wk by gavage. Rats received powderized chow and supplemental feeds to prevent the effects of malnutrition on bone composition. Weight gain and growth was restored after surgery in shunted animals. At termination, biochemical parameters of bone turnover and quantitative bone histology were assessed. Markers of T-cell activation, inflammatory cytokine production, and RANKL-dependent pathways were measured. In addition, the roles of IGF-1 and hypogonadism were investigated. Portasystemic shunting caused low turnover osteoporosis that was RANKL independent. Bone resorbing cytokine levels, including IL-1, IL-6 and TNFalpha, were not increased in serum and TNFalpha and RANKL expression were not upregulated in PBMC. Portasystemic shunting increased the circulating CD8+ T-cell population. Rapamycin decreased the circulating CD8+ T-cell population, increased CD8+ CD25+ T-regulatory cell population and improved all parameters of bone turnover. Osteoporosis caused by portasystemic shunting may be partially ameliorated by rapamycin in the rat model of hepatic osteodystrophy |
| Databáze: | OpenAIRE |
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