Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

YBX1 Promotes MSC Osteogenic Differentiation by Activating the PI3K/AKT Pathway

Author(s): Jiayu Chen, Zhanliang Liu, Huicheng Zhang, Yongqian Yang, Huangxiang Zeng, Rongwei Zhong, Shangdao Lai and Hongxing Liao*

Volume 18, Issue 4, 2023

Published on: 13 September, 2022

Page: [513 - 521] Pages: 9

DOI: 10.2174/1574888X17666220805143833

Price: $65

conference banner
Abstract

Introduction: Bone metabolism has an essential role in bone disease, but its specific mechanism remains unclear. Y-Box Binding Protein 1 (YBX1) is a gene with broad nucleic acid binding properties, which encodes a highly conserved cold shock domain protein. Previous studies have shown that YBX1 is closely related to cell differentiation. However, the function of YBX1 in osteoblast differentiation of bone marrow mesenchymal stem cells (MSCs) was unclear.

Methods: To explore the effect and specific mechanism of YBX1 in osteogenic differentiation of MSCs, we used PCR, Western blot, Alizarin red Staining, alkaline phosphatase (ALP) assays, and siRNA knockdown in our research. We found that YBX1 gradually increased during the process of osteogenic differentiation of MSCs. YBX1 siRNA could negatively regulate the MSCs osteogenic differentiation. Mechanistic studies revealed that YBX1 knockdown could inhibit PI3K/AKT pathway. Furthermore, the specific agonist (SC79) of PI3K/AKT pathway could restore the impaired MSCs osteogenic differentiation which was mediated by YBX1 knockdown. Taken together, we concluded that YBX1 could positively regulate the osteogenic differentiation of MSCs by activating the PI3K/AKT pathway.

Results and Discussion: These results helped us further understand the mechanism of osteogenesis and revealed that YBX1 might be a selectable target in the bone repair field.

Conclusion: Our study provides a new target and theoretical basis for the treatment of bone diseases.

Keywords: Bone metabolism, Y-Box Binding Protein, Alizarin red Staining, PI3K/AKT pathway, YBX1, osteogenesis.

« Previous Next »
[1]
Reid IR. A broader strategy for osteoporosis interventions. Nat Rev Endocrinol 2020; 16(6): 333-9.
[http://dx.doi.org/10.1038/s41574-020-0339-7] [PMID: 32203407]
[2]
Yang TL, Shen H, Liu A, et al. A road map for understanding molecular and genetic determinants of osteoporosis. Nat Rev Endocrinol 2020; 16(2): 91-103.
[http://dx.doi.org/10.1038/s41574-019-0282-7] [PMID: 31792439]
[3]
Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet 2019; 393(10169): 364-76.
[http://dx.doi.org/10.1016/S0140-6736(18)32112-3] [PMID: 30696576]
[4]
Dirckx N, Moorer MC, Clemens TL, Riddle RC. The role of osteoblasts in energy homeostasis. Nat Rev Endocrinol 2019; 15(11): 651-65.
[http://dx.doi.org/10.1038/s41574-019-0246-y] [PMID: 31462768]
[5]
Robling AG, Bonewald LF. The osteocyte: New insights. Annu Rev Physiol 2020; 82: 485-506.
[http://dx.doi.org/10.1146/annurev-physiol-021119-034332] [PMID: 32040934]
[6]
Al-Bari AA, Al Mamun A. Current advances in regulation of bone homeostasis. FASEB Bioadv 2020; 2(11): 668-79.
[http://dx.doi.org/10.1096/fba.2020-00058] [PMID: 33205007]
[7]
Kangari P, Talaei-Khozani T, Razeghian-Jahromi I, Razmkhah M. Mesenchymal stem cells: Amazing remedies for bone and cartilage defects. Stem Cell Res Ther 2020; 11(1): 492.
[http://dx.doi.org/10.1186/s13287-020-02001-1] [PMID: 33225992]
[8]
Kiernan J, Davies JE, Stanford WL. Concise review: Musculoskeletal stem cells to treat age-related osteoporosis. Stem Cells Transl Med 2017; 6(10): 1930-9.
[http://dx.doi.org/10.1002/sctm.17-0054] [PMID: 28834263]
[9]
Hu B, Lv X, Chen H, et al. Sensory nerves regulate mesenchymal stromal cell lineage commitment by tuning sympathetic tones. J Clin Invest 2020; 130(7): 3483-98.
[http://dx.doi.org/10.1172/JCI131554] [PMID: 32191640]
[10]
Zheng C, Sui B, Qiu X, Hu C, Jin Y. Mitochondrial regulation of stem cells in bone homeostasis. Trends Mol Med 2019.
[PMID: 31126872]
[11]
Iaquinta MR, Lanzillotti C, Mazziotta C, et al. The role of microRNAs in the osteogenic and chondrogenic differentiation of mesenchymal stem cells and bone pathologies. Theranostics 2021; 11(13): 6573-91.
[http://dx.doi.org/10.7150/thno.55664] [PMID: 33995677]
[12]
Codispoti B, Marrelli M, Paduano F, Tatullo M. NANOmetric BIO-Banked MSC-Derived Exosome (NANOBIOME) as a Novel Approach to Regenerative Medicine. J Clin Med 2018; 7(10): E357.
[http://dx.doi.org/10.3390/jcm7100357] [PMID: 30326618]
[13]
Tatullo M, Marrelli B, Zullo MJ, et al. Exosomes from human periapical Cyst-MSCs: Theranostic application in Parkinson’s disease. Int J Med Sci 2020; 17(5): 657-63.
[http://dx.doi.org/10.7150/ijms.41515] [PMID: 32210716]
[14]
Lyabin DN, Eliseeva IA, Ovchinnikov LP. YB-1 protein: Functions and regulation. Wiley Interdiscip Rev RNA 2014; 5(1): 95-110.
[http://dx.doi.org/10.1002/wrna.1200] [PMID: 24217978]
[15]
Suresh PS, Tsutsumi R, Venkatesh T. YBX1 at the crossroads of non-coding transcriptome, exosomal, and cytoplasmic granular signaling. Eur J Cell Biol 2018; 97(3): 163-7.
[http://dx.doi.org/10.1016/j.ejcb.2018.02.003] [PMID: 29478751]
[16]
Bates M, Boland A, McDermott N, Marignol L. YB-1: The key to personalised prostate cancer management? Cancer Lett 2020; 490: 66-75.
[http://dx.doi.org/10.1016/j.canlet.2020.07.006] [PMID: 32681926]
[17]
Yang F, Chen S, He S, Huo Q, Hu Y, Xie N. YB-1 interplays with ERα to regulate the stemness and differentiation of ER-positive breast cancer stem cells. Theranostics 2020; 10(8): 3816-32.
[http://dx.doi.org/10.7150/thno.41014] [PMID: 32206124]
[18]
Schmid R, Meyer K, Spang R, Schittek B, Bosserhoff AK. YBX1 is a modulator of MIA/CD-RAP-dependent chondrogenesis. PLoS One 2013; 8(12): e82166.
[http://dx.doi.org/10.1371/journal.pone.0082166] [PMID: 24349210]
[19]
Colter DC, Class R, DiGirolamo CM, Prockop DJ. Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow. Proc Natl Acad Sci USA 2000; 97(7): 3213-8.
[http://dx.doi.org/10.1073/pnas.97.7.3213] [PMID: 10725391]
[20]
Wagner W, Wein F, Seckinger A, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 2005; 33(11): 1402-16.
[http://dx.doi.org/10.1016/j.exphem.2005.07.003]
[21]
Weiss ARR, Dahlke MH. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs. Front Immunol 2019; 10: 1191.
[http://dx.doi.org/10.3389/fimmu.2019.01191] [PMID: 31214172]
[22]
Méndez-Ferrer S, Michurina TV, Ferraro F, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 2010; 466(7308): 829-34.
[http://dx.doi.org/10.1038/nature09262] [PMID: 20703299]
[23]
García-Sánchez D, Fernández D, Rodríguez-Rey JC, Pérez-Campo FM. Enhancing survival, engraftment, and osteogenic potential of mesenchymal stem cells. World J Stem Cells 2019; 11(10): 748-63.
[http://dx.doi.org/10.4252/wjsc.v11.i10.748] [PMID: 31692976]
[24]
Almalki SG, Agrawal DK. Key transcription factors in the differentiation of mesenchymal stem cells. Differentiation 2016; 92(1-2): 41-51.
[25]
Lorthongpanich C, Thumanu K, Tangkiettrakul K, et al. YAP as a key regulator of adipo-osteogenic differentiation in human MSCs. Stem Cell Res Ther 2019; 10(1): 402.
[http://dx.doi.org/10.1186/s13287-019-1494-4] [PMID: 31852542]
[26]
Sinha S, Biswas M, Chatterjee SS, Kumar S, Sengupta A. Pbrm1 Steers Mesenchymal Stromal Cell Osteolineage Differentiation by Integrating PBAF-Dependent Chromatin Remodeling and BMP/TGF-β Signaling. Cell Rep 2020; 31(4): 107570.
[http://dx.doi.org/10.1016/j.celrep.2020.107570] [PMID: 32348751]
[27]
Jeong BC, Kang IH, Hwang YC, Kim SH, Koh JT. MicroRNA-194 reciprocally stimulates osteogenesis and inhibits adipogenesis via regulating COUP-TFII expression. Cell Death Dis 2014; 5(11): e1532.
[http://dx.doi.org/10.1038/cddis.2014.485] [PMID: 25412310]
[28]
Cui Y, Li F, Xie Q, et al. YBX1 mediates autophagy by targeting p110β and decreasing the sensitivity to cisplatin in NSCLC. Cell Death Dis 2020; 11(6): 476.
[http://dx.doi.org/10.1038/s41419-020-2555-4] [PMID: 32561752]
[29]
Su H, Fan G, Huang J, Qiu X. YBX1 regulated by Runx3-miR-148a-3p axis facilitates non-small-cell lung cancer progression. Cell Signal 2021; 85: 110049.
[http://dx.doi.org/10.1016/j.cellsig.2021.110049] [PMID: 34082012]
[30]
Eliseeva IA, Kim ER, Guryanov SG, Ovchinnikov LP, Lyabin DN. Y-box-binding protein 1 (YB-1) and its functions. Biochemistry (Mosc) 2011; 76(13): 1402-33.
[http://dx.doi.org/10.1134/S0006297911130049] [PMID: 22339596]
[31]
Evans MK, Matsui Y, Xu B, et al. Ybx1 fine-tunes PRC2 activities to control embryonic brain development. Nat Commun 2020; 11(1): 4060.
[http://dx.doi.org/10.1038/s41467-020-17878-y] [PMID: 32792512]
[32]
Xu WF, Ma YC, Ma HS, et al. Co-targeting CK2α and YBX1 suppresses tumor progression by coordinated inhibition of the PI3K/AKT signaling pathway. Cell Cycle 2019; 18(24): 3472-90.
[http://dx.doi.org/10.1080/15384101.2019.1689474] [PMID: 31713447]
[33]
Kim A, Shim S, Kim YH, Kim MJ, Park S, Myung JK. Inhibition of Y Box Binding Protein 1 Suppresses Cell Growth and Motility in Colorectal Cancer. Mol Cancer Ther 2020; 19(2): 479-89.
[http://dx.doi.org/10.1158/1535-7163.MCT-19-0265] [PMID: 31672764]
[34]
Liu Z, Li Y, Li X, et al. Overexpression of YBX1 Promotes Pancreatic Ductal Adenocarcinoma Growth via the GSK3B/Cyclin D1/Cyclin E1 Pathway. Mol Ther Oncolytics 2020; 17: 21-30.
[http://dx.doi.org/10.1016/j.omto.2020.03.006] [PMID: 32300640]
[35]
Wang Y, Su J, Wang Y, et al. The interaction of YBX1 with G3BP1 promotes renal cell carcinoma cell metastasis via YBX1/G3BP1-SPP1- NF-κB signaling axis. J Exp Clin Cancer Res 2019; 38(1): 386.
[http://dx.doi.org/10.1186/s13046-019-1347-0] [PMID: 31481087]
[36]
Yang C, Liu X, Zhao K, et al. miRNA-21 promotes osteogenesis via the PTEN/PI3K/Akt/HIF-1α pathway and enhances bone regeneration in critical size defects. Stem Cell Res Ther 2019; 10(1): 65.
[http://dx.doi.org/10.1186/s13287-019-1168-2] [PMID: 30795815]
[37]
Ma Y, Ran D, Zhao H, et al. Cadmium exposure triggers osteoporosis in duck via P2X7/PI3K/AKT-mediated osteoblast and osteoclast differentiation. Sci Total Environ 2021; 750: 141638.
[http://dx.doi.org/10.1016/j.scitotenv.2020.141638] [PMID: 32858297]
[38]
Durbano HW, Halloran D, Nguyen J, et al. Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis. Int J Mol Sci 2020; 21(18): E6909.
[http://dx.doi.org/10.3390/ijms21186909] [PMID: 32967078]
[39]
Safari-Alighiarloo N, Taghizadeh M, Mohammad Tabatabaei S, Namaki S, Rezaei-Tavirani M. Identification of common key genes and pathways between type 1 diabetes and multiple sclerosis using transcriptome and interactome analysis. Endocrine 2020; 68(1): 81-92.
[http://dx.doi.org/10.1007/s12020-019-02181-8] [PMID: 31912409]
[40]
Bloch DB, Nobre RA, Yang WH. GW/P-bodies and autoimmune disease. Adv Exp Med Biol 2013; 768: 61-70.
[http://dx.doi.org/10.1007/978-1-4614-5107-5_5] [PMID: 23224965]

Rights & Permissions Print Cite
Article Metrics
59
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy