Abstract：Objective To explore irisin’s promotion mechanism of osteoblast differentiation of rabbit BMSCs in high glucose condition.Methods BMSCs of rabbit were divided into 4 groups: control, HG (high glucose), irisin (HG+irisin) and CQ (chloroquine; HG+irisin+CQ). After cultured in osteogenic differentiation medium for 5 days, western blotting was used to detect autophagy-related protein levels of P62 and LC3B; qRT-PCR was used to evaluate the expression levels of Runx2, ALP, COL-I and OCN; ALP activity was also tested.Results Compared with the control group, HG group significantly increased P62 and decreased LC3B-II protein levels, down-regulated mRNA expression of Runx2, ALP and COL-I, and reduced ALP activity (P＜0.05);however, irisin obviously decreased P62 and increased LC3B-II protein levels, up-regulated mRNA expression of Runx2, ALP and COL-I, and promoted ALP activity (P＜0.05); moreover, when inhibited autophagy with CQ, the effect of irisin was blunted (P＜0.05).Conclusion Irisin promotes osteoblast differentiation of BMSCs in high glucose condition via activating autophagy.
Li R, Wang X, Wu S, et al. Irisin ameliorates angiotensin II-induced cardiomyocyte apoptosis through autophagy[J]. J Cell Physiol, 2019,234(10):17578-17588.
[7]
Bi J, Yang L, Wang T, et al. Irisin improves autophagy of aged hepatocytes via increasing telomerase activity in liver injury[J]. Oxid Med Cell Longev, 2020,2020:6946037.
[8]
Chen X, Sun K, Zhao S, et al. Irisin promotes osteogenic differentiation of bone marrow mesenchymal stem cells by activating autophagy via the Wnt/β-catenin signal pathway[J]. Cytokine, 2020,136:155292.
[9]
Ye X, Shen Y, Ni C, et al. Irisin reverses insulin resistance in C2C12 cells via the p38-MAPK-PGC-1α pathway[J]. Peptides, 2019,119:170120.
[10]
Lu J, Xiang G, Liu M, et al. Irisin protects against endothelial injury and ameliorates atherosclerosis in apolipoprotein E-Null diabetic mice[J]. Atherosclerosis, 2015,243(2):438-448.
[11]
Zhu B, Li Y, Mei W, et al. Alogliptin improves endothelial function by promoting autophagy in perivascular adipose tissue of obese mice through a GLP-1-dependent mechanism[J]. Vascul Pharmacol, 2019,115:55-63.
Polyzos S A, Kountouras J, Anastasilakis A D, et al. Irisin in patients with nonalcoholic fatty liver disease[J]. Metabolism, 2014,63(2):207-217.
[15]
Liu S, Du F, Li X, et al. Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells[J]. PLoS One, 2017,12(4):e175498.
[16]
Song H, Wu F, Zhang Y, et al. Irisin promotes human umbilical vein endothelial cell proliferation through the ERK signaling pathway and partly suppresses high glucose-induced apoptosis[J]. PLoS One, 2014,9(10):e110273.
[17]
Li R L, Wu S S, Wu Y, et al. Irisin alleviates pressure overload-induced cardiac hypertrophy by inducing protective autophagy via mTOR-independent activation of the AMPK-ULK1 pathway[J]. J Mol Cell Cardiol, 2018,121:242-255.
Rubinsztein D C, Mario G, Kroemer G. Autophagy and aging[J]. Cell, 2011,146(5):682-695.
[20]
Wan Y, Zhuo N, Li Y, et al. Autophagy promotes osteogenic differentiation of human bone marrow mesenchymal stem cell derived from osteoporotic vertebrae[J]. Biochem Biophys Res Commun, 2017,488(1):46-52.
[21]
Huang Z, Nelson E R, Smith R L, et al. The sequential expression profiles of growth factors from osteoprogenitors [correction of osteroprogenitors] to osteoblasts in vitro[J]. Tissue Eng, 2007,13(9):2311-2320.
[22]
Vilchez D, Saez I, Dillin A. The role of protein clearance mechanisms in organismal ageing and age-related diseases[J]. Nat Commun, 2014,5:5659.
[23]
Lee I H, Cao L, Mostoslavsky R, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy[J]. Proc Natl Acad Sci U S A, 2008,105(9):3374-3379.
2022, Vol. 33 
