Blockade of IL‐33 signalling attenuates osteoarthritis
Abstract Objectives Osteoarthritis (OA) is the most common form of arthritis characterised by cartilage degradation, synovitis and pain. Disease modifying treatments for OA are not available. The critical unmet need is to find therapeutic targets to reduce both disease progression and pain. The cyto...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Clinical & Translational Immunology |
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| Online Access: | https://doi.org/10.1002/cti2.1187 |
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| author | Zengliang He Yan Song Yongxiang Yi Fengzhuo Qiu Junhua Wang Junwei Li Qingwen Jin Pradeep Kumar Sacitharan |
| author_facet | Zengliang He Yan Song Yongxiang Yi Fengzhuo Qiu Junhua Wang Junwei Li Qingwen Jin Pradeep Kumar Sacitharan |
| author_sort | Zengliang He |
| collection | DOAJ |
| description | Abstract Objectives Osteoarthritis (OA) is the most common form of arthritis characterised by cartilage degradation, synovitis and pain. Disease modifying treatments for OA are not available. The critical unmet need is to find therapeutic targets to reduce both disease progression and pain. The cytokine IL‐33 and its receptor ST2 have been shown to play a role in immune and inflammatory diseases, but their role in osteoarthritis is unknown. Methods Non‐OA and OA human chondrocytes samples were examined for IL‐33 and ST2 expression. Novel inducible cartilage specific knockout mice (IL‐33Acan CreERT2) and inducible fibroblast‐like synoviocyte knockout mice (IL‐33Col1a2 CreERT2) were generated and subjected to an experimental OA model. In addition, wild‐type mice were intra‐articularly administered with either IL‐33‐ or ST2‐neutralising antibodies during experimental OA studies. Results IL‐33 and its receptor ST2 have increased expression in OA patients and a murine disease model. Administering recombinant IL‐33 increased OA and pain in vivo. Synovial fibroblast‐specific deletion of IL‐33 decreased synovitis but did not impact disease outcomes, whilst cartilage‐specific deletion of IL‐33 improved disease outcomes in vivo. Blocking IL‐33 signalling also reduced the release of cartilage‐degrading enzymes in human and mouse chondrocytes. Most importantly, we show the use of monoclonal antibodies against IL‐33 and ST2 attenuates both OA and pain in vivo. Conclusion Overall, our data reveal blockade of IL‐33 signalling as a viable therapeutic target for OA. |
| first_indexed | 2024-12-23T04:34:17Z |
| format | Article |
| id | doaj.art-12f8b8fb3c784c27bc57d3244370ebf6 |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-12-23T04:34:17Z |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-12f8b8fb3c784c27bc57d3244370ebf62022-12-21T17:59:56ZengWileyClinical & Translational Immunology2050-00682020-01-01910n/an/a10.1002/cti2.1187Blockade of IL‐33 signalling attenuates osteoarthritisZengliang He0Yan Song1Yongxiang Yi2Fengzhuo Qiu3Junhua Wang4Junwei Li5Qingwen Jin6Pradeep Kumar Sacitharan7Department of Orthopedics The Second Hospital of Nanjing The Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing ChinaDepartment of Orthopedics The Second Hospital of Nanjing The Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing ChinaDepartment of General Surgery The Second Hospital of Nanjing The Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing ChinaDepartment of Neurology The Sir Run Run Hospital Nanjing Medical University Nanjing ChinaCollege of Veterinary Medicine Qingdao Agricultural University Qingdao ChinaCollege of Veterinary Medicine Qingdao Agricultural University Qingdao ChinaDepartment of Neurology The Sir Run Run Hospital Nanjing Medical University Nanjing ChinaThe Institute of Ageing and Chronic Disease University of Liverpool Liverpool UKAbstract Objectives Osteoarthritis (OA) is the most common form of arthritis characterised by cartilage degradation, synovitis and pain. Disease modifying treatments for OA are not available. The critical unmet need is to find therapeutic targets to reduce both disease progression and pain. The cytokine IL‐33 and its receptor ST2 have been shown to play a role in immune and inflammatory diseases, but their role in osteoarthritis is unknown. Methods Non‐OA and OA human chondrocytes samples were examined for IL‐33 and ST2 expression. Novel inducible cartilage specific knockout mice (IL‐33Acan CreERT2) and inducible fibroblast‐like synoviocyte knockout mice (IL‐33Col1a2 CreERT2) were generated and subjected to an experimental OA model. In addition, wild‐type mice were intra‐articularly administered with either IL‐33‐ or ST2‐neutralising antibodies during experimental OA studies. Results IL‐33 and its receptor ST2 have increased expression in OA patients and a murine disease model. Administering recombinant IL‐33 increased OA and pain in vivo. Synovial fibroblast‐specific deletion of IL‐33 decreased synovitis but did not impact disease outcomes, whilst cartilage‐specific deletion of IL‐33 improved disease outcomes in vivo. Blocking IL‐33 signalling also reduced the release of cartilage‐degrading enzymes in human and mouse chondrocytes. Most importantly, we show the use of monoclonal antibodies against IL‐33 and ST2 attenuates both OA and pain in vivo. Conclusion Overall, our data reveal blockade of IL‐33 signalling as a viable therapeutic target for OA.https://doi.org/10.1002/cti2.1187chondrocytesIL‐33inflammationosteoarthritisST2 |
| spellingShingle | Zengliang He Yan Song Yongxiang Yi Fengzhuo Qiu Junhua Wang Junwei Li Qingwen Jin Pradeep Kumar Sacitharan Blockade of IL‐33 signalling attenuates osteoarthritis Clinical & Translational Immunology chondrocytes IL‐33 inflammation osteoarthritis ST2 |
| title | Blockade of IL‐33 signalling attenuates osteoarthritis |
| title_full | Blockade of IL‐33 signalling attenuates osteoarthritis |
| title_fullStr | Blockade of IL‐33 signalling attenuates osteoarthritis |
| title_full_unstemmed | Blockade of IL‐33 signalling attenuates osteoarthritis |
| title_short | Blockade of IL‐33 signalling attenuates osteoarthritis |
| title_sort | blockade of il 33 signalling attenuates osteoarthritis |
| topic | chondrocytes IL‐33 inflammation osteoarthritis ST2 |
| url | https://doi.org/10.1002/cti2.1187 |
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