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Effects of angiotensin-converting enzyme inhibitor,captopril, on bone of mice with streptozotocin-induced type 1 diabetes |
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| Authors: | Teng-Yue Diao Hai Pan Sa-Sa Gu Xi Chen Fang-Yi Zhang Man-Sau Wong Yan Zhang |
| Affiliation: | 1. Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China 2. School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China 3. State Key Laboratory of Bio-control, National Engineering Center of South China Sea for Marine Biotechnology, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Higher Education Mega Center, Sun Yat-sen University, Guangzhou, 510006, People’s Republic of China 4. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, People’s Republic of China |
| Abstract: | There are contradictory results about the effect of angiotensin-converting enzyme inhibitors (ACEIs) on bone. This study was performed to address the skeletal renin?angiotensin system (RAS) activity and the effects of the ACEI, captopril, on the bone of streptozotocin-induced type 1 diabetic mice. Histochemical assessment on bone paraffin sections was conducted by Safranin O staining and tartrate-resistant acid phosphatase staining. Micro-computed tomography was performed to analyze bone biological parameters. Gene and protein expression were determined by real-time polymerase chain reaction and immunoblotting, respectively. Type 1 diabetic mice displayed osteopenia phenotype and captopril treatment showed no osteoprotective effects in diabetic mice as shown by the reduction of bone mineral density, trabecular thickness and bone volume/total volume. The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril. However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-β and osteocalcin mRNA expression in the tibia compared to those of diabetic mice. The present study demonstrated that the use of the ACEI, captopril, has no beneficial effect on the skeletal biological properties of diabetic mice. However, this could be attributed, at least partially, to its suppression of osteogenesis and stimulation of osteoclastogenesis, even though it could effectively inhibit high activity of local RAS in the bone of diabetic mice. |
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