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Anti-inflammatory Effect of DNA Polymeric Molecules in a Cell Model of Osteoarthritis

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Abstract

The DNA polymeric molecules polydeoxynucleotide (PDRN) and polynucleotide (PN) can be used as new alternative treatment for osteoarthritis (OA); however, the underlying mechanisms are not fully understood. In this study, we investigated the effect of PDRN and PN on gene-expression profiles in a cell model of OA using transcriptome analysis. Under hypoxic conditions, human chondrosarcoma cells were stressed for 24 h in the presence of interleukin (IL)-1β and subsequently treated with PDRN, PN, or hyaluronic acid (HA) for another 24 h, followed by transcriptome analysis. The results of the transcriptome study comprising differentially expressed genes were analyzed using the Database of Annotation Visualization and Integrated Discovery program, which yielded Kyoto Encyclopedia of Genes and Genomes pathways. Toll-like receptor (TLR)- and nucleotide-binding oligomerization domain-like receptor (NLR)-signaling pathways were related between the IL-1β group and the group treated with DNA polymeric molecules. The genes involved in the TLR- and NLR-signaling pathways were validated using real-time quantitative polymerase chain reaction and western blot. Among these genes, IL-6, IL-1β, IL-8, and chemokine (C-C motif) ligand 3 were dramatically upregulated in the IL-1β group, but significantly downregulated in the group treated with DNA polymeric molecules. Specifically, PN treatment resulted in a greater decrease in the expression of these genes as compared with PDRN treatment. Both PDRN and PN treatments were involved in the anti-inflammatory response associated with OA progression, with PN treatment exhibiting additional anti-inflammatory properties relative to PDRN treatment. These results provide insight into potential therapeutic approaches involving PDRN and PN treatment of OA.

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Abbreviations

OA:

osteoarthritis

PDRN:

polydeoxynucleotide

PN:

polynucleotide

NOD:

nucleotide-binding oligomerization domain

NLR:

nucleotide-binding oligomerization domain-like receptor

HA:

hyaluronic acid

PBS:

phosphate-buffered saline

DMEM-HG:

dulbecco’s modified Eagle medium-high glucose

DAVID:

Database for Annotation, Visualization, and Integrated Discovery

KEGG:

Kyoto Encyclopedia of Genes and Genomes

RT-PCR:

reverse transcription polymerase chain reaction

qRT-PCR:

real-time quantitative PCR

IL:

interleukin

CCL:

chemokine (C-C motif) ligand

CXCL:

C-X-C motif chemokine

LBP:

lipopolysaccharide-binding protein

TLR:

toll-like receptor

TNFAIP3:

tumor necrosis factor alpha-induced protein 3

CASP:

caspase apoptosis-related cysteine peptidase

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

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Acknowledgments

This research was supported by grants from the National Research Foundation (2015M3A9B4067068, and 2017R1D1A1B03028855); the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1012); and by EMBRI Grants 2015EMBRI SN0005 from the Eulji University.

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Authors and Affiliations

  1. Department and Rehabilitation Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea

    Ahreum Baek & Sung Hoon Kim

  2. Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South Korea

    Ahreum Baek, MinGi Kim & Sung-Rae Cho

  3. Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea

    MinGi Kim & Sung-Rae Cho

  4. Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, Republic of Korea

    Sung-Rae Cho

  5. Department of Rehabilitation Medicine, Nowon Eulji Medical Center, Eulji University, Seoul, Republic of Korea

    Hyun Jung Kim

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  1. Ahreum Baek
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  2. MinGi Kim
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Contributions

A.B. contributed to study conception and design, collection and/or assembly of data, and manuscript writing; M.G.K. contributed to manuscript writing; S.H.K. contributed to manuscript writing; and S.R.C. and H.J.K contributed to data analysis and interpretation, manuscript writing, and project supervision. All authors read and approved the manuscript.

Corresponding authors

Correspondence to Sung-Rae Cho or Hyun Jung Kim.

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Electronic supplementary material

Supplementary Table 1

Raw data for 18,892 differentially expressed transcripts. (XLSX 5279 kb)

Supplementary Table 2

Raw data for 185 differentially expressed transcripts. (XLSX 36 kb)

Supplementary Table 3

Raw data for 99 differentially expressed transcripts. (XLSX 23 kb)

Supplementary Table 4

Raw data for 44 differentially expressed transcripts. (XLSX 16 kb)

Supplementary Table 5

Raw data for 43 differentially expressed transcripts. (XLSX 16 kb)

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Baek, A., Kim, M., Kim, S.H. et al. Anti-inflammatory Effect of DNA Polymeric Molecules in a Cell Model of Osteoarthritis. Inflammation 41, 677–688 (2018). https://doi.org/10.1007/s10753-017-0722-2

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  • DOI: https://doi.org/10.1007/s10753-017-0722-2

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