Lycium barbarum polysaccharide (LBP) inhibits palmitic acid (PA)-induced MC3T3-E1 cell apoptosis by regulating miR-200b-3p/Chrdl1/PPARγ
Background: Obesity is closely related to osteoporosis. Lycium barbarum polysaccharides (LBPs) have anti- osteoporosis activity.
Objective: This study aimed to explore the role of LBPs in palmitic acid (PA)-induced osteoblast apoptosis.
Methods: The microarray data set GSE37676 was downloaded from Gene Expression Ominibus (GEO) database. Top 300 differentially expressed genes (DEGs) were used to construct a protein–protein interaction (PPI) network based on STRING database, and significant modules were analyzed and their key genes were screened by using Cytoscape software. COEXPEDIA database showed that there was co-expression between Chrdl1 and peroxisome proliferator-activated receptor (PPARγ). MC3T3-E1 cells were treated with 100–500 μg/mL of PA. Reverse transcription polymerase chain reaction (RT-PCR) and western blot assays were used to detect mRNA and protein levels. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were used to detect cell viability and cell apoptosis.
Results: Chrdl1 was the key gene from the most significant module and downregulation in MC3T3-E1 cells treated with PA. MicroRNA miR-200b-3p and PPARγ were significantly upregulated among PA-treated MC3T3-E1 cells. The results of luciferase reporter gene assay showed that miR-200b-3p targeted Chrdl1 3’-UTR. Over-expressing miR-200b-3p promoted PA-induced cell apoptosis and inhibited cell viability. After pre-treating cells with PA and LBP, MC3T3-E1 cell apoptosis rate was relatively lower than that of mimics+PA200 group. Chrdl1 inhibition partly reversed miR-200b-3p effect on inhibiting apoptosis among MC3T3-E1 cells pre-treated with LBP and PA. Decreased C CASP3, PPARγ and increased Chrdl1 by miR- 200b-3p inhibition were partly reversed by Chrdl1 inhibition.
Conclusions: LBPs inhibit PA-induced MC3T3-E1 cell apoptosis by mainly decreasing miR-200b-3p to upregulate Chrdl1, but miR-200b-3p/Chrdl1/PPARγ is not the only mechanism for LBPs protecting osteoblasts from PA.
- Fassio A, Idolazzi L, Rossini M, Gatti D, Adami G, Giollo A, et al. The obesity paradox and osteoporosis. Eating and weight disorders: Eat Weight Disord (EWD) 2018;23(3):293–302. doi: 10.1007/s40519-018-0505-2
- Candido FG, Bressan J. Vitamin D: link between osteoporosis, obesity, and diabetes? Int J Mol Sci 2014;15(4):6569–91. doi: 10.3390/ijms15046569
- Chen L, Wang G, Wang Q, Liu Q, Sun Q, Chen L. N-acetylcysteine prevents orchiectomy-induced osteoporosis by inhibiting oxidative stress and osteocyte senescence. Am J Tran Res 2019;11(7):4337–47.
- Abourehab MAS, Hussain Z. Hyaluronic acid modified risedronate and teriparatide co-loaded nanocarriers for improved osteogenic differentiation of osteoblasts for treatment of osteoporosis. Curr Pharm Des 2019;25(27):2975–88. doi: 10.2174/1381612825666190801140703
- Wang T, He C, Yu X. Pro-inflammatory cytokines: new potential therapeutic targets for obesity-related bone disorders. Curr Drug Target 2017;18(14):1664–75. doi: 10.2174/1389450118666170104153512
- Picke AK, Campbell GM, Bluher M, Krugel U, Schmidt FN, Tsourdi E, et al. Thy-1 (CD90) promotes bone formation and protects against obesity. Sci Transl Med 2018;10(453):eaao6806. doi: 10.1126/scitranslmed.aao6806
- Liang W, Yue Z. Lycium barbarum polysaccharides promote osteoblasts viability by regulating microRNA-17/PTEN. Life Sci 2019;225:72–8. doi: 10.1016/j.lfs.2019.04.001
- Liu Q, Han Q, Lu M, Wang H, Tang F. Lycium barbarum polysaccharide attenuates cardiac hypertrophy, inhibits calpain-1 expression and inhibits NF-kappaB activation in streptozotocin-induced diabetic rats. Exp Ther Med 2019;18(1):509–16. doi: 10.3892/etm.2019.7612
- Xiao J, Xing F, Huo J, Fung ML, Liong EC, Ching YP, et al. Lycium barbarum polysaccharides therapeutically improve hepatic functions in non-alcoholic steatohepatitis rats and cellular steatosis model. Sci Rep 2014;4:5587. doi: 10.1038/srep05587
- Puhl AC, Milton FA, Cvoro A, Sieglaff DH, Campos JC, Bernardes A, et al. Mechanisms of peroxisome proliferator activated receptor gamma regulation by non-steroidal anti-inflammatory drugs. Nucl Receptor Signal 2015;13:e004. doi: 10.1621/nrs.13004
- Jing L, Jia XW. Lycium barbarum polysaccharide arbitrates palmitate-induced apoptosis in MC3T3E1 cells through decreasing the activation of ERS-mediated apoptosis pathway. Mol Med Rep 2018;17(2):2415–21. doi: 10.3892/mmr.2017.8128
- Ho KH, Cheng CH, Chou CM, Chen PH, Liu AJ, Lin CW, et al. miR-140 targeting CTSB signaling suppresses the mesenchymal transition and enhances temozolomide cytotoxicity in glioblastoma multiforme. Pharmacol Res 2019;147(9):147–104390. doi: 10.1016/j.phrs.2019.104390
- Huang J, Wang S, Feng X, Liu X, Zhao J, Zheng Q, et al. miRNA transcriptome comparison between muscle and adipose tissues indicates potential miRNAs associated with intramuscular fat in Chinese swamp buffalo. Genome 2019;62(11):729–38. doi: 10.1139/gen-2018-0178
- Chen R, Qiu H, Tong Y, Liao F, Hu X, Qiu Y, et al. MiRNA-19a-3p alleviates the progression of osteoporosis by targeting HDAC4 to promote the osteogenic differentiation of hMSCs. Biochem Biophy Res Comm 2019;516(3):666–72. doi: 10.1016/j.bbrc.2019.06.083
- Chen Y, Yang YR, Fan XL, Lin P, Yang H, Chen XZ, et al. miR-206 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells by targetting glutaminase. Biosci Rep 2019;39(3):BSR20181108. doi: 10.1042/bsr20181108
- Li Z, Hassan MQ, Jafferji M, Aqeilan RI, Garzon R, Croce CM, et al. Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem 2009;284(23):15676–84. doi: 10.1074/jbc.M809787200
- Chen Y, Zhang F, Zhao Y, He K, Zheng X, Pan Y, et al. Obesity-associated miR-27a upregulation promotes hepatocellular carcinoma metastasis through suppressing SFRP1. Onco Target Ther 2018;11:3281–92. doi: 10.2147/ott.s162978
- Baselga-Escudero L, Arola-Arnal A, Pascual-Serrano A, Ribas-Latre A, Casanova E, Salvado MJ, et al. Chronic administration of proanthocyanidins or docosahexaenoic acid reverses the increase of miR-33a and miR-122 in dyslipidemic obese rats. PLoS One 2013;8(7):e69817. doi: 10.1371/journal.pone.0069817
- Kim S, Lee MS, Jung S, Son HY, Park S, Kang B, et al. Ginger extract ameliorates obesity and inflammation via regulating microRNA-21/132 expression and AMPK activation in white adipose tissue. Nutrients 2018;10(11):1567. doi: 10.3390/nu10111567
- Li D, Wang H, Song H, Xu H, Zhao B, Wu C, et al. The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells. Oncotarget 2017;8(49):85276–89. doi: 10.18632/oncotarget.19205
- Wu J, Tao Y, Shang A, Wang W, Zhang Y, Hu L, et al. Effect of the interaction between MiR-200b-3p and DNMT3A on cartilage cells of osteoarthritis patients. J Cell Mol Med 2017;21(10):2308–16. doi: 10.1111/jcmm.13152
- Zhu J, Zhao LH, Chen Z. [Stimulation by Lycium bararum polysaccharides of the maturation of dendritic cells in murine bone marrow]. Zhejiang da xue xue bao Yi xue ban. J Zhejiang Univ Med Sci 2006;35(6):648–52.
- Mock K, Preca BT, Brummer T, Brabletz S, Stemmler MP, Brabletz T. The EMT-activator ZEB1 induces bone metastasis associated genes, including BMP-inhibitors. Oncotarget 2015;6(16):14399–412. doi: 10.18632/oncotarget.3882
- Cyr-Depauw C, Northey JJ, Tabaries S, Annis MG, Dong Z, Cory S, et al. Chordin-like 1 suppresses bone morphogenetic protein 4-induced breast cancer cell migration and invasion. Mol Cell Biol 2016;36(10):1509–25. doi: 10.1128/mcb.00600-15
- Pei YF, Zhang YJ, Lei Y, Wu DW, Ma TH, Liu XQ. Correction: hypermethylation of the CHRDL1 promoter induces proliferation and metastasis by activating Akt and Erk in gastric cancer. Oncotarget 2017;8(29):48526. doi: 10.18632/oncotarget.19303
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright of their work, with first publication rights granted to SNF Swedish Nutrition Foundation. Read the full Copyright- and Licensing Statement.