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Home / Equine Research Bank / Int J Mol Sci / Functionalized Nanogels with Endothelin-1 and Bradykinin Rec...
International journal of molecular sciences2022; 23(16); 8949; doi: 10.3390/ijms23168949

Functionalized Nanogels with Endothelin-1 and Bradykinin Receptor Antagonist Peptides Decrease Inflammatory and Cartilage Degradation Markers of Osteoarthritis in a Horse Organoid Model of Cartilage.

Abstract: Osteoarthritis (OA) is a degenerative and heterogeneous disease that affects all types of joint structures. Current clinical treatments are only symptomatic and do not manage the degenerative process in animals or humans. One of the new orthobiological treatment strategies being developed to treat OA is the use of drug delivery systems (DDS) to release bioactive molecules over a long period of time directly into the joint to limit inflammation, control pain, and reduce cartilage degradation. Two vasoactive peptides, endothelin-1 and bradykinin, play important roles in OA pathogenesis. In this study, we investigated the effects of two functionalized nanogels as DDS. We assessed the effect of chitosan functionalized with a type A endothelin receptor antagonist (BQ-123-CHI) and/or hyaluronic acid functionalized with a type B bradykinin receptor antagonist (R-954-HA). The biocompatibility of these nanogels, alone or in combination, was first validated on equine articular chondrocytes cultured under different oxic conditions. Further, in an OA equine organoid model via induction with interleukin-1 beta (IL-1β), a combination of BQ-123-CHI and R-954-HA (BR5) triggered the greatest decrease in inflammatory and catabolic markers. In basal and OA conditions, BQ-123-CHI alone or in equimolar combinations with R-954-HA had weak pro-anabolic effects on collagens synthesis. These new nanogels, as part of a composite DDS, show promising attributes for treating OA.
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Publication Date: 2022-08-11 PubMed ID: 36012214PubMed Central: PMC9408731DOI: 10.3390/ijms23168949Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explored the use of functionalized nanogels loaded with peptides known to counteract inflammation and cartilage degradation, in order to treat Osteoarthritis (OA) in a horse model. The study found that these nanogels triggered a significant decrease in destructive biomarkers of OA, demonstrating their potential for future use in OA treatment.

Research Objective and Background

  • The main aim of this study was to investigate the potential of functionalized nanogels, loaded with specific peptides, as a long-term drug delivery system (DDS) for treating Osteoarthritis (OA).
  • OA is a degenerative disease affecting joint structures in both animals and humans. Despite existing treatments, there is no cure, and these treatments only manage symptoms rather than halt disease progression.
  • This research is significant as it explores the development of a new orthobiological treatment strategy that could effectively manage the degradation process associated with OA.

Methodology

  • Two types of nanogels were developed: a chitosan nanogel functionalized with a type A endothelin receptor antagonist (BQ-123-CHI), and a hyaluronic acid nanogel functionalized with a type B bradykinin receptor antagonist (R-954-HA).
  • The researchers first tested the biocompatibility of these nanogels on equine articular chondrocytes, which are the cells responsible for maintaining joint cartilage.
  • The effects of the nanogels were then assessed in an OA equine organoid model, which was induced with an inflammatory cytokine (IL-1β) known to exacerbate OA.

Findings

  • The research found that a combination of BQ-123-CHI and R-954-HA showed the greatest decrease in inflammatory and catabolic markers related to OA.
  • The study also found that BQ-123-CHI, either alone or combined with R-954-HA in equimolar amounts, had a low but positive impact on the synthesis of collagens—critical proteins for maintaining joint health and integrity.
  • Overall, these nanogels demonstrated promise as a component of a DSS aimed at managing OA, due to their ability to reduce inflammation, control pain, and prevent cartilage degradation.

Implications

  • The use of functionalized nanogels as DDS could revolutionize the weak fields of OA treatment by providing a customized, targeted and long-lasting treatment method.
  • This research also hints at the possibility of expanding the application of these nanogels to other joint diseases that have similar pathological mechanisms.
  • However, more comprehensive studies are required, including in vivo models and clinical trials, to fully understand the effectiveness, safety, and potential side effects of this treatment strategy.

Cite This Article

APA
Cullier A, Cassé F, Manivong S, Contentin R, Legendre F, Garcia Ac A, Sirois P, Roullin G, Banquy X, Moldovan F, Bertoni L, Audigié F, Galéra P, Demoor M. (2022). Functionalized Nanogels with Endothelin-1 and Bradykinin Receptor Antagonist Peptides Decrease Inflammatory and Cartilage Degradation Markers of Osteoarthritis in a Horse Organoid Model of Cartilage. Int J Mol Sci, 23(16), 8949. https://doi.org/10.3390/ijms23168949

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 23
Issue: 16
PII: 8949

Researcher Affiliations

Cullier, Aurélie
  • Normandie University, UNICAEN, BIOTARGEN, 14000 Caen, France.
Cassé, Frédéric
  • Normandie University, UNICAEN, BIOTARGEN, 14000 Caen, France.
Manivong, Seng
  • Research Center of CHU Sainte Justine, Montreal, QC H3T 1C5, Canada.
  • Faculty of Dentistry, Université de Montréal, Montreal, QC H3T 1J4, Canada.
  • Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada.
Contentin, Romain
  • Normandie University, UNICAEN, BIOTARGEN, 14000 Caen, France.
Legendre, Florence
  • Normandie University, UNICAEN, BIOTARGEN, 14000 Caen, France.
Garcia Ac, Aracéli
  • Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada.
  • TransMedTech Institute (NanoBio Technology Platform), Montreal, QC H3T 1J4, Canada.
Sirois, Pierre
  • Department of Microbiology and Immunology, Faculty of Medicine, Université de Laval, Q City, QC G1V 4G2, Canada.
Roullin, Gaëlle
  • Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada.
Banquy, Xavier
  • Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada.
Moldovan, Florina
  • Research Center of CHU Sainte Justine, Montreal, QC H3T 1C5, Canada.
  • Faculty of Dentistry, Université de Montréal, Montreal, QC H3T 1J4, Canada.
Bertoni, Lélia
  • Center of Imaging and Research on Locomotor Affections in Equines, Veterinary School of Alfort, 14430 Goustranville, France.
Audigié, Fabrice
  • Center of Imaging and Research on Locomotor Affections in Equines, Veterinary School of Alfort, 14430 Goustranville, France.
Galéra, Philippe
  • Normandie University, UNICAEN, BIOTARGEN, 14000 Caen, France.
Demoor, Magali
  • Normandie University, UNICAEN, BIOTARGEN, 14000 Caen, France.

MeSH Terms

  • Animals
  • Bradykinin Receptor Antagonists / metabolism
  • Bradykinin Receptor Antagonists / pharmacology
  • Bradykinin Receptor Antagonists / therapeutic use
  • Cartilage / metabolism
  • Cartilage, Articular / metabolism
  • Cells, Cultured
  • Chondrocytes / metabolism
  • Endothelin-1 / metabolism
  • Horses
  • Humans
  • Interleukin-1beta / metabolism
  • Nanogels
  • Organoids / metabolism
  • Osteoarthritis / metabolism

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 2 times.
  1. Narayanan KB, Bhaskar R, Han SS. Recent Advances in the Biomedical Applications of Functionalized Nanogels.. Pharmaceutics 2022 Dec 16;14(12).
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