Effects of angiotensin-converting enzyme inhibitor, captopril, on bone of mice with streptozotocin-induced type 1 diabetes.
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.
Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, 200093, People's Republic of China.
Teng-Yue
TY
Diao
Hai
H
Pan
Sa-Sa
SS
Gu
Xi
X
Chen
Fang-Yi
FY
Zhang
Man-Sau
MS
Wong
Yan
Y
Zhang
D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000235:genetics; D001851:Bone Diseases, Metabolic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002216:Captopril / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013311:Streptozocin; D000071681:Tartrate-Resistant Acid Phosphatase; D013977:Tibia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007527:Isoenzymes; D016328:NF-kappa B; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D000804:Angiotensin II; D013311:Streptozocin; D002216:Captopril; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D012083:Renin