The Role of MicroRNAs in Early Chondrogenesis of Human Induced Pluripotent Stem Cells (hiPSCs)

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Sep 8

PMID 31492046

Citations 14

Authors

Ewelina Stelcer

Katarzyna Kulcenty

Marcin Rucinski

Karol Jopek

Magdalena Richter

Tomasz Trzeciak

Wiktoria Maria Suchorska

Affiliations

Soon will be listed here.

Abstract

Human induced pluripotent stem cells (hiPSCs) play an important role in research regarding regenerative medicine. Particularly, chondrocytes differentiated from hiPSCs seems to be a promising solution for patients suffering from osteoarthritis. We decided to perform chondrogenesis in a three-week monolayer culture. Based on transcriptome analysis, hiPSC-derived chondrocytes (ChiPS) demonstrate the gene expression profile of cells from early chondrogenesis. Chondrogenic progenitors obtained by our group are characterized by significantly high expression of Hox genes, strongly upregulated during limb formation and morphogenesis. There are scanty literature data concerning the role of microRNAs in early chondrogenesis, especially in chondrogenic differentiation of hiPSCs. The main aim of this study was to investigate the microRNA expression profile and to select microRNAs (miRNAs) taking part in early chondrogenesis. Our findings allowed for selection crucial miRNAs engaged in both diminishing pluripotency state and chondrogenic process (inter alia hsa-miR-525-5p, hsa-miR-520c-3p, hsa-miR-628-3p, hsa-miR-196b-star, hsa-miR-629-star, hsa-miR-517b, has-miR-187). These miRNAs regulate early chondrogenic genes such as: , , , . These results were confirmed by RT-qPCR analysis. This work contributes to a better understanding of the role of miRNAs directly involved in chondrogenic differentiation of hiPSCs. These data may result in the establishment of a more efficient protocol of obtaining chondrocyte-like cells from hiPSCs.

Citing Articles

Mogroside V enhances bone marrow mesenchymal stem cells osteogenesis under hyperglycemic conditions through upregulating miR-10b-5p and PI3K/Akt signaling.

Lan D, Li K, Ye Z, Luo Y, Li C, Li H J Orthop Surg Res. 2025; 20(1):278.

PMID: 40082984 PMC: 11907933. DOI: 10.1186/s13018-025-05684-5.

Differentiation of stem cells into chondrocytes and their potential clinical application in cartilage regeneration.

Ciesla J, Tomsia M Histochem Cell Biol. 2025; 163(1):27.

PMID: 39863760 DOI: 10.1007/s00418-025-02356-7.

Transcriptomic analyses and machine-learning methods reveal dysregulated key genes and potential pathogenesis in human osteoarthritic cartilage.

Zhao D, Zeng L, Liang G, Luo M, Pan J, Dou Y Bone Joint Res. 2024; 13(2):66-82.

PMID: 38310924 PMC: 10838620. DOI: 10.1302/2046-3758.132.BJR-2023-0074.R1.

Mesenchymal Stem Cells Cultured in a 3D Microgel Environment Containing Platelet-Rich Plasma Significantly Modify Their Chondrogenesis-Related miRNA Expression.

Mata M, Salvador-Clavell R, Rodenas-Rochina J, Sancho-Tello M, Gallego Ferrer G, Ribelles J Int J Mol Sci. 2024; 25(2).

PMID: 38256011 PMC: 10815493. DOI: 10.3390/ijms25020937.

CircRNA/lncRNA-miRNA-mRNA network and gene landscape in calcific aortic valve disease.

Zheng Y, Wen S, Jiang S, He S, Qiao W, Liu Y BMC Genomics. 2023; 24(1):419.

PMID: 37491214 PMC: 10367311. DOI: 10.1186/s12864-023-09441-y.

References

Suchorska W, Augustyniak E, Richter M, Trzeciak T . Comparison of Four Protocols to Generate Chondrocyte-Like Cells from Human Induced Pluripotent Stem Cells (hiPSCs). Stem Cell Rev Rep. 2016; 13(2):299-308. PMC: 5380716. DOI: 10.1007/s12015-016-9708-y. View

Wang T, Shi S, Sha H . MicroRNAs in regulation of pluripotency and somatic cell reprogramming: small molecule with big impact. RNA Biol. 2013; 10(8):1255-61. PMC: 3817145. DOI: 10.4161/rna.25828. View

Stelcer E, Kulcenty K, Rucinski M, Jopek K, Richter M, Trzeciak T . Chondrogenic differentiation in vitro of hiPSCs activates pathways engaged in limb development. Stem Cell Res. 2018; 30:53-60. DOI: 10.1016/j.scr.2018.05.006. View

Yamashita A, Tamamura Y, Morioka M, Karagiannis P, Shima N, Tsumaki N . Considerations in hiPSC-derived cartilage for articular cartilage repair. Inflamm Regen. 2018; 38:17. PMC: 6171247. DOI: 10.1186/s41232-018-0075-8. View

Nejadnik H, Diecke S, Lenkov O, Chapelin F, Donig J, Tong X . Improved approach for chondrogenic differentiation of human induced pluripotent stem cells. Stem Cell Rev Rep. 2015; 11(2):242-53. PMC: 4412587. DOI: 10.1007/s12015-014-9581-5. View

Guerit D, Brondello J, Chuchana P, Philipot D, Toupet K, Bony C . FOXO3A regulation by miRNA-29a Controls chondrogenic differentiation of mesenchymal stem cells and cartilage formation. Stem Cells Dev. 2014; 23(11):1195-205. DOI: 10.1089/scd.2013.0463. View

Jopek K, Tyczewska M, Celichowski P, Malendowicz L, Rucinski M . Transcriptome Profile in Unilateral Adrenalectomy-Induced Compensatory Adrenal Growth in the Rat. Int J Mol Sci. 2018; 19(4). PMC: 5979382. DOI: 10.3390/ijms19041111. View

Wang A, Ren M, Song Y, Wang X, Wang Q, Yang Q . MicroRNA Expression Profiling of Bone Marrow Mesenchymal Stem Cells in Steroid-Induced Osteonecrosis of the Femoral Head Associated with Osteogenesis. Med Sci Monit. 2018; 24:1813-1825. PMC: 5887684. DOI: 10.12659/msm.909655. View

Gautier L, Cope L, Bolstad B, Irizarry R . affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004; 20(3):307-15. DOI: 10.1093/bioinformatics/btg405. View

10.

Kang Y, Zhang Z, Zhang H, Duan X, Liu J, Li X . Expression of microRNAs during chondrogenesis of human adipose-derived stem cells. Osteoarthritis Cartilage. 2012; 20(12):1638-46. DOI: 10.1016/j.joca.2012.08.024. View

11.

Dimitrion P, Zhi Y, Clayton D, Apodaca G, Wilcox M, Johnson J . Low-Density Neuronal Cultures from Human Induced Pluripotent Stem Cells. Mol Neuropsychiatry. 2017; 3(1):28-36. PMC: 5582512. DOI: 10.1159/000476034. View

12.

Barter M, Tselepi M, Gomez R, Woods S, Hui W, Smith G . Genome-Wide MicroRNA and Gene Analysis of Mesenchymal Stem Cell Chondrogenesis Identifies an Essential Role and Multiple Targets for miR-140-5p. Stem Cells. 2015; 33(11):3266-80. PMC: 4737122. DOI: 10.1002/stem.2093. View

13.

Yekta S, Shih I, Bartel D . MicroRNA-directed cleavage of HOXB8 mRNA. Science. 2004; 304(5670):594-6. DOI: 10.1126/science.1097434. View

14.

Mahboudi H, Soleimani M, Enderami S, Kehtari M, Ardeshirylajimi A, Eftekhary M . Enhanced chondrogenesis differentiation of human induced pluripotent stem cells by MicroRNA-140 and transforming growth factor beta 3 (TGFβ3). Biologicals. 2018; 52:30-36. DOI: 10.1016/j.biologicals.2018.01.005. View

15.

Benjamini Y, Cohen R . Weighted false discovery rate controlling procedures for clinical trials. Biostatistics. 2016; 18(1):91-104. PMC: 5255051. DOI: 10.1093/biostatistics/kxw030. View

16.

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

17.

Kitada M, Wakao S, Dezawa M . Muse cells and induced pluripotent stem cell: implication of the elite model. Cell Mol Life Sci. 2012; 69(22):3739-50. PMC: 3478511. DOI: 10.1007/s00018-012-0994-5. View

18.

Dennis Jr G, Sherman B, Hosack D, Yang J, Gao W, Lane H . DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003; 4(5):P3. View

19.

Chen S, Xu Z, Shao J, Fu P, Wu H . MicroRNA-218 promotes early chondrogenesis of mesenchymal stem cells and inhibits later chondrocyte maturation. BMC Biotechnol. 2019; 19(1):6. PMC: 6334453. DOI: 10.1186/s12896-018-0496-0. View

20.

Stelcer E, Kulcenty K, Rucinski M, Jopek K, Trzeciak T, Richter M . Expression of Pluripotency Genes in Chondrocyte-Like Cells Differentiated from Human Induced Pluripotent Stem Cells. Int J Mol Sci. 2018; 19(2). PMC: 5855772. DOI: 10.3390/ijms19020550. View