期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 320, 期 1, 页码 E55-E70出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00158.2020
关键词
angiotensin II; angiotensin (1-7); diabetes; osteoblast; osteoclast
资金
- National Natural Science Foundation of China [81774329, 82074468]
- Essential Drug Research and Development [2019ZX09201004-003-032]
- National Key RD Program [2018YFC1704302]
- Program for Innovative Research Team from Ministry of Science and Technology of China [2015RA4002]
- Hundred Talents Program from Shanghai Municipal Commission of Health and Family Planning [2018BR03]
- Program of Shanghai Academic Research Leader [19XD1423800]
- Natural Science Foundation of Shanghai [17ZR1430800]
- Sanming Project of Medicine in Shenzhen [SZSM201808072]
In this study, it was found that ANG II and ANG(1-7) had different effects on osteoblasts and osteoclasts under high-glucose conditions, playing different roles in the development of osteoporosis, with ANG(1-7) showing a protective effect against diabetes-induced osteoporosis.
Osteoporosis, diabetes, and hypertension are common concurrent chronic disorders. This study aimed to explore the respective effects of angiotensin II (ANG II) and angiotensin(1-7) [ANG(1-7)], active peptides in the renin-angiotensin system, on osteoblasts and osteoclasts under high-glucose level, as well as to investigate the osteo-preservative effects of ANG II type 1 receptor (AT1R) blocker and ANG(1-7) in diabetic spontaneously hypertensive rats (SHR). ANG II and ANG(1-7), respectively, decreased and increased the formation of calcified nodules and alkaline phosphatase activity in MC3T3-E1 cells under high-glucose level, and respectively stimulated and inhibited the number of matured osteoclasts and pit resorptive area in RANKL-induced bone marrow macrophages. Olmesartan and Mas receptor antagonist A779 could abolish those effects. ANG II and ANG(1-7), respectively, downregulated and upregulated the expressions of osteogenesis factors in MC3T3-E1 cells. ANG II promoted the expressions of cathepsin K and MMP9 in RAW 264.7 cells, whereas ANG(1-7) repressed these osteoclastogenesis factors. ANG II rapidly increased the phosphorylation of Akt and p38 in RAW 264.7 cells, whereas ANG(1-7) markedly reduced the phosphorylation of p38 and ERK under high-glucose condition. After treatments of diabetic SHR with valsartan and ANG(1-7), a significant increase in trabecular bone area, bone mineral density, and mechanical strength was only found in the ANG(1-7)-treated group. Treatment with ANG(1-7) significantly suppressed the increase in renin expression and ANG II content in the bone of SHR. Taken together, ANG II/AT1R and ANG(1-7)/Mas distinctly regulated the differentiation and functions of osteoblasts and osteoclasts upon exposure to high-glucose condition. ANG(1-7) could protect SHR from diabetes-induced osteoporosis.
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