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Cited by 36Osteoarthritis Treatment and MechanismsProteoglycans and glycosaminoglycans researchPeriodontal Regeneration and Treatments

Polynucleotides Suppress Inflammation and Stimulate Matrix Synthesis in an In Vitro Cell-Based Osteoarthritis Model

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Kuppa, Sree Samanvitha, Kim, Hyung-Keun, Kang, Ju-Yeon, Lee, Seok-Cheol, Yang, Hong-Yeol, Sankaranarayanan, Jaishree, Seon, Jong-Keun·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms241512282PMC PMC10418450
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Abstract

Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell hypertrophy in human articular chondrocytes (HC-a) by activating the NF-κB pathway. Chondrocyte hypertrophy and inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control and regulate cell hypertrophy as well as to maintain the ECM. The involvement of these two pathways is crucial for preserving the homeostasis of articular cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged as a promising area of research for the treatment of OA. PN-HPT involves the use of polynucleotide-based agents with controlled natural origins and high purification levels. In this study, we focused on evaluating the efficacy of a specific polynucleotide sodium agent, known as CONJURAN, which is derived from fish sperm. Polynucleotides (PN), which are physiologically present in the matrix and function as water-soluble nucleic acids with a gel-like property, have been used to treat patients with OA. However, the specific mechanisms underlying the effect remain unclear. Therefore, we investigated the effect of PN in an OA cell model in which HC-a cells were stimulated with interleukin−1β (IL−1β) with or without PN treatment. The CCK-8 assay was used to assess the cytotoxic effects of PN. Furthermore, the enzyme-linked immunosorbent assay was utilized to detect MMP13 levels, and the nitric oxide assay was utilized to determine the effect of PN on inflammation. The anti-inflammatory effects of PN and related mechanisms were investigated using quantitative PCR, Western blot analysis, and immunofluorescence to examine and analyze relative markers. PN inhibited IL−1β induced destruction of genes and proteins by downregulating the expression of MMP3, MMP13, iNOS, and COX-2 while increasing the expression of aggrecan (ACAN) and collagen II (COL2A1). This study demonstrates, for the first time, that PN exerted anti-inflammatory effects by partially inhibiting the NF-κB pathway and increasing the Smad2/3 pathway. Based on our findings, PN can potentially serve as a treatment for OA.

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  • PN has shown favorable outcomes in improving knee function and alleviating pain without causing serious adverse effects.

    “In addition, PN has shown favorable outcomes in improving knee function and alleviating pain without causing serious adverse effects [42,43,44,45,46,47].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [43]

    The Introduction (p. unavailable) reports that intra-articular PN reduces pain and improves function in patients with knee osteoarthritis. The Discussion (p. unavailable) describes minimal adverse effects and a low risk of adverse effects, but this in vitro study does not establish that patients experienced no serious adverse effects. (LLM, conf=0.83)

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Sorted by citations

Authors
Kuppa, S. S., Kim, H.-K., Kang, J.-Y., Lee, S.-C., Yang, H.-Y., Sankaranarayanan, J., & Seon, J.-K.
Affiliations
  • Chonnam National University (KR)
  • Chonnam National University Hospital (KR)
Corresponding author
Seon, Jong-Keun
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-07-31
Volume
24
Issue
15
Pages
12282
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms241512282
PMC
PMC10418450
OpenAlex
W4385446474
Cited by
36
References
2
Citations by year
2026: 9 · 2025: 14 · 2024: 11 · 2023: 2
FWCI
7.54
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Korea government (the Ministry of Science and ICT, the Ministry of Health & Welfare) (22C0603L1-11)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
Keywords
osteoarthritis, polynucleotides, articular chondrocytes, chondrocyte hypertrophy, NF-κB signaling, Smad2/3 signaling, IL-1β, matrix metalloproteinases, MMP-13, MMP-3, inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, extracellular matrix degradation, aggrecan, type II collagen, anti-inflammatory activity, cartilage homeostasis
MeSH terms
Animals, Anti-Inflammatory Agents, Cells, Cultured, Humans, Hypertrophy, Inflammation, Male, Osteoarthritis, Polynucleotides, Semen, NF-kappa B, Chondrocytes, Matrix Metalloproteinase 13, Interleukin-1beta

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