Journal of Diagnostics Concepts & Practice >

2022 , Vol. 21 >Issue 03: 367 - 373

DOI: https://doi.org/10.16150/j.1671-2870.2022.03.013

Original articles

Transcriptome study of glucagon like peptide-1 agonist Exendin-4 on mouse embryonic osteoblast precursor MC3T3-E1 in vitro

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  • Department of Endocrinology and Metabolism, Dongying People′s Hospital, Shandong Dongying 257091, China

Received date: 2022-02-01

  Online published: 2022-08-17

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Abstract

Objective: To observe the effects of Exendin-4, a glucagon-like peptide-1(GLP-1) receptor agonist, on proliferation and osteogenic differentiation of Mc3t3-E1(mouse embryonic osteoblast precursor cells) in vitro. Methods: Mc3t3-E1 cells were treated with Exendin-4 at a pre-experimental concentration of 30 nmol/L for 72 h. The cells were collected for sequencing, and the RNA-SEQ data were obtained. The differentially expressed genes greater than 2 times were screened and KEGG PATHWAY enrichment analysis and GO enrichment analysis were performed. Results: Mc3t3-E1 cells were proliferated after Exendin-4 treatment, and a total of 418 differentially expressed genes were screened, including 236 up-regulated genes and 182 down-regulated genes. GO enrichment analysis showed that the up-regulated differentially expressed genes were mainly enriched in the immune system, cellular adhesion and proteolytic pathways. KEGG PATHWAY enrichment analysis showed that The down-regulated differentially expressed genes were mainly enriched in PI3K-Akt signaling pathway, abnormal transcription in cancer, mammalian target of Rapamycin (mTOR) receptor signaling pathway, and hypoxia inducible factor 1 (HYPO xia inducible) Factor-1, HIF-1) signaling pathway. It revealed that up-regulated genes related to osteoporosis included Fosl1, Cxcl13, Clec11a, Phex, Fasl, Camk4, Stab1, Zbp1, Adora2a, Igfbp7, Cxcr2, Hp, MTI; while for Down-regulated genes included Nog, Zeb1, Esr1, Igf2bp2, Plxnb3, Rgs14. Conclusions: Exendin-4 can affect the differentiation of precursor cells into osteoblasts by influencing the expression levels of gene related to cell immunity, cell adhesion and proteolysis related genes, and ultimately affect the formation and development of osteoporosis.

Key words： Cell proliferation; Exendin-4; Osteoblast; Osteoporosis; RNA-Seq

Cite this article

LIU Xin, QI Caihui, WANG Zhenjing, LÜ Na, WANG Shaoting, WANG Shuping . Transcriptome study of glucagon like peptide-1 agonist Exendin-4 on mouse embryonic osteoblast precursor MC3T3-E1 in vitro[J]. Journal of Diagnostics Concepts & Practice, 2022 , 21(03) : 367 -373 . DOI: 10.16150/j.1671-2870.2022.03.013

References

[1] Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects[J]. J Clin Invest, 2005, 115(12):3318-3325.
[2] 中华医学会骨质疏松和骨矿盐疾病分会. 原发性骨质疏松症诊疗指南(2017)[J]. 中国骨质疏松杂志, 2019, 25(3):281-309.
[2] Osteoporosis and bone mineral Disease Branch of Chinese Medical Association. Guidelines for the diagnosis and management of primary osteoporosis (2017)[J]. Chin J Osteoporos, 2019, 25(3):281-309.
[3] 朱洁云, 高敏, 宋秋韵, 等. 中国老年人骨质疏松症患病率的Meta分析[J]. 中国全科医学, 2022, 25(3):346-353.
[3] Zhu JY, Gao M, Song QY, et al. Prevalence of Osteoporosis in Chinese Elderly People: a Meta-analysis[J]. Chin Gen Pract, 2022, 25(3):346-353.
[4] Drucker DJ. Minireview: the glucagon-like peptides[J]. Endocrinology, 2001, 142(2):521-527.
[5] Ma X, Meng J, Jia M, et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, prevents osteopenia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats[J]. J Bone Miner Res, 2013, 28(7):1641-1652.
[6] Gao L, Li S, Li Y. Exendin-4 promotes the osteogenic differentiation of osteoblasts via the Hedgehog/Gli1 signaling pathway[J]. Am J Transl Res, 2018, 10(1):315-324.
[7] Chen JH, Shen C, Oh H, et al. Exendin-4, a glucagon-like peptide receptor agonist, facilitates osteoblast diffe-rentiation via connexin43[J]. Endocrine, 2021, 72(3):672-680.
[8] Manolagas SC. Birth and death of bone cells: basic regu-latory mechanisms and implications for the pathogenesis and treatment of osteoporosis[J]. Endocr Rev, 2000, 21(2):115-137.
[9] Xie B, Chen S, Xu Y, et al. The Impact of Glucagon-like peptide 1 receptor agonists on bone metabolism and its possible mechanisms in osteoporosis treatment[J]. Front Pharmacol, 2021, 12:697442.
[10] Nuche-Berenguer B, Lozano D, Gutiérrez-Rojas I, et al. GLP-1 and exendin-4 can reverse hyperlipidic-related osteopenia[J]. J Endocrinol, 2011, 209(2):203-210.
[11] Feng Y, Su L, Zhong X, et al. Exendin-4 promotes proli-feration and differentiation of MC3T3-E1 osteoblasts by MAPKs activation[J]. J Mol Endocrinol, 2016, 56(3):189-199.
[12] Guder C, Gravius S, Burger C, et al. Osteoimmunology: a current update of the interplay between bone and the immune system[J]. Front Immunol, 2020, 11:58.
[13] Lerner UH. Osteoclasts in health and disease[J]. Pediatr Endocrinol Rev, 2019, 17(2):84-99.
[14] 邓禹, 黄禾, 金鸿雁. 绝经后女性骨质疏松相关基因的生物信息学分析[J]. 生殖医学杂志, 2021, 30(10):1341-1348.
[14] Deng Y, Huang H, Jin HY. Bioinformatics analysis of osteoporosis-related genes in postmenopausal women[J]. J Reprod Med, 2021, 30(10):1341-1348.
[15] Pereira RC, Canalis E. Parathyroid hormone increases mac25/insulin-like growth factor-binding protein-related protein-1 expression in cultured osteoblasts[J]. Endocrino-logy, 1999, 140(5):1998-2003.
[16] Ye C, Hou W, Chen M, et al. IGFBP7 acts as a negative regulator of RANKL-induced osteoclastogenesis and oestrogen deficiency-induced bone loss[J]. Cell Prolif, 2020, 53(2):e12752.
[17] Chen Z, Li L, Wu W, et al. Exercise protects proliferative muscle satellite cells against exhaustion via the Igfbp7-Akt-mTOR axis[J]. Theranostics, 2020, 10(14):6448-6466.
[18] 陈亚辉, 龚忠勤, 崔燎. PI3 K/Akt 信号通路在骨质疏松病理过程中的作用[J]. 中国骨质疏松杂志, 2015(3):356-360.
[18] Chen YH, Gong ZQ, Cui L. Effect of PI3K/Akt pathway on the pathological development of osteoporosis[J]. Chin J Osteoporos, 2015(3):356-360.
[19] Tateishi K, Nakamura T, Juratli TA, et al. PI3K/AKT/mTOR pathway alterations promote malignant progression and xenograft formation in oligodendroglial tumors[J]. Clin Cancer Res, 2019, 25(14):4375-4387.
[20] 陈露华, 唐宏宇. 补骨脂素对绝经后大鼠骨质疏松及PI3K/Akt/mTOR信号通路的影响[J]. 中国药房, 2021, 32(6):697-701.
[20] Chen LH, Tang HY. Effect of Psoralen on Osteoporosis in postmenopausal rats and PI3K/Akt/mTOR signaling pathway[J]. China Pharm, 2021, 32(6):697-701.
[21] Baniwal SK, Shah PK, Shi Y, et al. Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2 mesenchymal progenitor cells[J]. Osteoporos Int, 2012, 23(4):1399-1413.
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