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
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 O...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/8949 |
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| author | Aurélie Cullier Frédéric Cassé Seng Manivong Romain Contentin Florence Legendre Aracéli Garcia Ac Pierre Sirois Gaëlle Roullin Xavier Banquy Florina Moldovan Lélia Bertoni Fabrice Audigié Philippe Galéra Magali Demoor |
| author_facet | Aurélie Cullier Frédéric Cassé Seng Manivong Romain Contentin Florence Legendre Aracéli Garcia Ac Pierre Sirois Gaëlle Roullin Xavier Banquy Florina Moldovan Lélia Bertoni Fabrice Audigié Philippe Galéra Magali Demoor |
| author_sort | Aurélie Cullier |
| collection | DOAJ |
| description | 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<sub>1</sub> 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. |
| first_indexed | 2024-03-09T13:18:40Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:18:40Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9fd7288185954154a236df3741beb2fb2023-11-30T21:32:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316894910.3390/ijms23168949Functionalized Nanogels with Endothelin-1 and Bradykinin Receptor Antagonist Peptides Decrease Inflammatory and Cartilage Degradation Markers of Osteoarthritis in a Horse Organoid Model of CartilageAurélie Cullier0Frédéric Cassé1Seng Manivong2Romain Contentin3Florence Legendre4Aracéli Garcia Ac5Pierre Sirois6Gaëlle Roullin7Xavier Banquy8Florina Moldovan9Lélia Bertoni10Fabrice Audigié11Philippe Galéra12Magali Demoor13Normandie University, UNICAEN, BIOTARGEN, 14000 Caen, FranceNormandie University, UNICAEN, BIOTARGEN, 14000 Caen, FranceResearch Center of CHU Sainte Justine, Montreal, QC H3T 1C5, CanadaNormandie University, UNICAEN, BIOTARGEN, 14000 Caen, FranceNormandie University, UNICAEN, BIOTARGEN, 14000 Caen, FranceFaculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, CanadaDepartment of Microbiology and Immunology, Faculty of Medicine, Université de Laval, Quebec City, QC G1V 4G2, CanadaFaculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, CanadaFaculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, CanadaResearch Center of CHU Sainte Justine, Montreal, QC H3T 1C5, CanadaCenter of Imaging and Research on Locomotor Affections in Equines, Veterinary School of Alfort, 14430 Goustranville, FranceCenter of Imaging and Research on Locomotor Affections in Equines, Veterinary School of Alfort, 14430 Goustranville, FranceNormandie University, UNICAEN, BIOTARGEN, 14000 Caen, FranceNormandie University, UNICAEN, BIOTARGEN, 14000 Caen, FranceOsteoarthritis (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<sub>1</sub> 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.https://www.mdpi.com/1422-0067/23/16/8949chondrocyteequine modeldrug delivery systembradykininendothelin-1chitosan |
| spellingShingle | Aurélie Cullier Frédéric Cassé Seng Manivong Romain Contentin Florence Legendre Aracéli Garcia Ac Pierre Sirois Gaëlle Roullin Xavier Banquy Florina Moldovan Lélia Bertoni Fabrice Audigié Philippe Galéra Magali Demoor 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 International Journal of Molecular Sciences chondrocyte equine model drug delivery system bradykinin endothelin-1 chitosan |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | chondrocyte equine model drug delivery system bradykinin endothelin-1 chitosan |
| url | https://www.mdpi.com/1422-0067/23/16/8949 |
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