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Differential responses of bone to angiotensin II and angiotensin(1-7): beneficial effects of ANG(1-7) on bone with exposure to high glucose.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2021 Jan 01; Vol. 320 (1), pp. E55-E70. Date of Electronic Publication: 2020 Oct 26. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- 3T3 Cells
Angiotensin II Type 1 Receptor Blockers pharmacology
Animals
Bone Density drug effects
Bone Development drug effects
Male
Mice
Osteoblasts drug effects
Osteoclasts drug effects
Osteoporosis prevention & control
Phosphorylation drug effects
RAW 264.7 Cells
Rats
Rats, Inbred SHR
Angiotensin I pharmacology
Angiotensin II pharmacology
Bone Density Conservation Agents pharmacology
Bone and Bones drug effects
Glucose adverse effects
Peptide Fragments pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 320
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 33103451
- Full Text :
- https://doi.org/10.1152/ajpendo.00158.2020