ATAC-seq Reveals the Roles of Chromatin Accessibility in the Chondrocytes of Kashin-Beck Disease Compared with Primary Osteoarthritis

Overview

Journal Front Genet

Date 2023 Jun 8

PMID 37287534

Authors

Sen Wang

Yuanji Wang

Xingyu Li

Linlin Yuan

Xiong Guo

Mikko J Lammi

Affiliations

Soon will be listed here.

Abstract

This study aimed to investigate the roles of accessible chromatin in understanding the different pathogeneses between Kashin-Beck disease (KBD) and primary osteoarthritis (OA). Articular cartilages of KBD and OA patients were collected, and after tissue digestion, primary chondrocytes were cultured . Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) was performed to compare the accessible chromatin differences of chondrocytes between KBD and OA groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were executed for the promoter genes. Then, the IntAct online database was used to generate networks of significant genes. Finally, we overlapped the analysis of differentially accessible region (DAR)-associated genes and differentially expressed genes (DEGs) obtained from whole-genomic microarray. We obtained 2,751 total DARs, which contained 1,985 loss and 856 gain DARs and belonged to 11 location distributions. We obtained 218 motifs associated with loss DARs, 71 motifs associated with gain DARs, 30 motif enrichments of loss DARs, and 30 motif enrichments of gain DARs. In total, 1,749 genes are associated with loss DARs, and 826 genes are associated with gain DARs. Among them, 210 promoter genes are associated with loss DARs, and 112 promoter genes are associated with gain DARs. We obtained 15 terms of GO enrichment and 5 terms of KEGG pathway enrichment from loss DAR promoter genes, and 15 terms of GO enrichment and 3 terms of KEGG pathway enrichment from gain DAR promoter genes. We obtained CAPN6 and other 2 overlap genes from loss DARs-vs-down DEGs, AMOTL1 from gain DARs-vs-down DEGs, EBF3 and other 12 overlap genes from loss DARs-vs-up DEGs, and ADARB1 and other 10 overlap genes from 101 gain DARs-vs-up DEGs. These overlap genes were built into 4 gene interaction networks. and were the overlapped genes from the DAR-associated genes and DEGs. These genes were associated with the abnormal chondrocyte function, which may play crucial roles in different processes between KBD and OA in the way of accessible chromatin.

Citing Articles

ATAC-seq for Characterizing Host and Pathogen Genome Accessibility During Virus Infection.

Liu D, Howard T, Cristea I Methods Mol Biol. 2024; 2866:111-122.

PMID: 39546200 DOI: 10.1007/978-1-0716-4192-7_7.

References

Kelly T, Souza A, Clish C, Puigserver P . A hypoxia-induced positive feedback loop promotes hypoxia-inducible factor 1alpha stability through miR-210 suppression of glycerol-3-phosphate dehydrogenase 1-like. Mol Cell Biol. 2011; 31(13):2696-706. PMC: 3133367. DOI: 10.1128/MCB.01242-10. View

Nagy A, Kenesi E, Rentsendorj O, Molnar A, Szenasi T, Sinko I . Evolutionarily conserved, growth plate zone-specific regulation of the matrilin-1 promoter: L-Sox5/Sox6 and Nfi factors bound near TATA finely tune activation by Sox9. Mol Cell Biol. 2010; 31(4):686-99. PMC: 3028657. DOI: 10.1128/MCB.00019-10. View

Zhang F, Lammi M, Shao W, Zhang P, Zhang Y, Wei H . Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T Inhibit Toxicity of HT-2?. Toxins (Basel). 2019; 11(11). PMC: 6891367. DOI: 10.3390/toxins11110667. View

Wang S, Gao Z, Liu H, Meng P, Wu C, Lammi M . Roles of glycoprotein glycosylation in the pathogenesis of an endemic osteoarthritis, Kashin–Beck disease, and effectiveness evaluation of sodium hyaluronate treatment. Turk J Med Sci. 2019; 50(4):1028-1037. PMC: 7379414. DOI: 10.3906/sag-1903-137. View

Galang G, Mandla R, Ruan H, Jung C, Sinha T, Stone N . ATAC-Seq Reveals an Enhancer That Regulates Sinoatrial Node Development and Function. Circ Res. 2020; 127(12):1502-1518. PMC: 7720845. DOI: 10.1161/CIRCRESAHA.120.317145. View

Buenrostro J, Wu B, Chang H, Greenleaf W . ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide. Curr Protoc Mol Biol. 2015; 109:21.29.1-21.29.9. PMC: 4374986. DOI: 10.1002/0471142727.mb2129s109. View

Pan D, Qian B, Zhao D, Yao B . Nfib promotes chondrocyte proliferation and inhibits differentiation by mildly regulating Sox9 and its downstream genes. Mol Biol Rep. 2021; 48(11):7487-7497. DOI: 10.1007/s11033-021-06767-2. View

Jiang Y, Zhang L, Tian H . MicroRNA-149 improves osteoarthritis via repression of VCAM-1 and inactivation of PI3K/AKT pathway. Exp Gerontol. 2023; 174:112103. DOI: 10.1016/j.exger.2023.112103. View

Sun Y, Mauerhan D, Honeycutt P, Kneisl J, Norton J, Hanley Jr E . Analysis of meniscal degeneration and meniscal gene expression. BMC Musculoskelet Disord. 2010; 11:19. PMC: 2828422. DOI: 10.1186/1471-2474-11-19. View

10.

Guo X, Ma W, Zhang F, Ren F, Qu C, Lammi M . Recent advances in the research of an endemic osteochondropathy in China: Kashin-Beck disease. Osteoarthritis Cartilage. 2014; 22(11):1774-83. DOI: 10.1016/j.joca.2014.07.023. View

11.

Lazarus J, Hegde A, Andrade A, Nilsson O, Baron J . Fibroblast growth factor expression in the postnatal growth plate. Bone. 2006; 40(3):577-86. DOI: 10.1016/j.bone.2006.10.013. View

12.

Zhang F, Luo W, Lei G . Role of HIF-1α and HIF-2α in osteoarthritis. Joint Bone Spine. 2015; 82(3):144-7. DOI: 10.1016/j.jbspin.2014.10.003. View

13.

Harasymowicz N, Azfer A, Burnett R, Simpson H, Salter D . Chondrocytes from osteoarthritic cartilage of obese patients show altered adiponectin receptors expression and response to adiponectin. J Orthop Res. 2021; 39(11):2333-2339. DOI: 10.1002/jor.24993. View

14.

Zhai X, Meng R, Li H, Li J, Jing L, Qin L . miR-181a Modulates Chondrocyte Apoptosis by Targeting Glycerol-3-Phosphate Dehydrogenase 1-Like Protein (GPD1L) in Osteoarthritis. Med Sci Monit. 2017; 23:1224-1231. PMC: 5360418. DOI: 10.12659/msm.899228. View

15.

Zhang D, Deng X, Liu Y, Zhang Y, Wang H, Zhang M . MMP-10 Deficiency Effects Differentiation and Death of Chondrocytes Associated with Endochondral Osteogenesis in an Endemic Osteoarthritis. Cartilage. 2022; 13(3):19476035221109226. PMC: 9280830. DOI: 10.1177/19476035221109226. View

16.

Wang S, Duan C, Zhang F, Ma W, Guo X . Regulatory gene networks and signaling pathways from primary osteoarthritis and Kashin-Beck disease, an endemic osteoarthritis, identified by three analysis software. Gene. 2012; 512(1):89-96. DOI: 10.1016/j.gene.2012.10.006. View

17.

Tsuchida S, Arai Y, Takahashi K, Kishida T, Terauchi R, Honjo K . HIF-1α-induced HSP70 regulates anabolic responses in articular chondrocytes under hypoxic conditions. J Orthop Res. 2014; 32(8):975-80. DOI: 10.1002/jor.22623. View

18.

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

19.

Zhang Y, Liu T, Meyer C, Eeckhoute J, Johnson D, Bernstein B . Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008; 9(9):R137. PMC: 2592715. DOI: 10.1186/gb-2008-9-9-r137. View

20.

Uchihashi T, Kimata M, Tachikawa K, Koshimizu T, Okada T, Ihara-Watanabe M . Involvement of nuclear factor I transcription/replication factor in the early stage of chondrocytic differentiation. Bone. 2007; 41(6):1025-35. DOI: 10.1016/j.bone.2007.08.028. View