Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway
IntroductionAlthough biomaterials strategies have been regarded as a promising approach for the treatment of osteoarthritis (OA), identifying novel drugs to be delivered for modulate macrophage polarization is still unclear. As a commonly used non-steroidal anti-inflammatory drug for OA, Imrecoxib m...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1526092/full |
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| author | Peng Peng Peng Peng Peng Peng Wanling Zheng Yuchen Liu Jingyuan Huang Bin Zhang Jiawei Shen Jiangang Cao |
| author_facet | Peng Peng Peng Peng Peng Peng Wanling Zheng Yuchen Liu Jingyuan Huang Bin Zhang Jiawei Shen Jiangang Cao |
| author_sort | Peng Peng |
| collection | DOAJ |
| description | IntroductionAlthough biomaterials strategies have been regarded as a promising approach for the treatment of osteoarthritis (OA), identifying novel drugs to be delivered for modulate macrophage polarization is still unclear. As a commonly used non-steroidal anti-inflammatory drug for OA, Imrecoxib may be a novel drug to direct and sustain macrophage phenotype. However, the specific protective mechanism of Imrecoxib in OA remains unclear. This study aims to investigate whether Imrecoxib would treat OA by regulating synovial macrophage polarization.MethodsThe research involves constructing mouse destabilization of medial meniscus (DMM) model to assess the changes in pain, bone destruction, cartilage degeneration, and synovial macrophage phenotypes following Imrecoxib treatment. Additionally, the effects of macrophage conditioned medium (CM) pretreated with Imrecoxib on the chondrocyte apoptosis, inflammation and degeneration-related factor expression were evaluated. The role of COX-2/PGE2 signaling pathway in the macrophage phenotype changes was further investigated.ResultsWe found that Imrecoxib alleviated pain, cartilage degeneration and synovitis, promoted polarization of M1 macrophages toward M2 phenotype in vivo and in vitro. In vitro experiments, Imrecoxib-CM protected chondrocyte by modulating macrophage polarization. Furthermore, Imrecoxib regulates macrophage polarization through the COX-2/PGE2 pathway.ConclusionThis study unravels that Imrecoxib protects joint cartilage and attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway, providing new drug delivery strategy for the clinical treatment of OA. |
| format | Article |
| id | doaj-art-c88250d3f65746ef8494459623f929cb |
| institution | Kabale University |
| issn | 2296-4185 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj-art-c88250d3f65746ef8494459623f929cb2025-08-20T03:53:43ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-04-011310.3389/fbioe.2025.15260921526092Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathwayPeng Peng0Peng Peng1Peng Peng2Wanling Zheng3Yuchen Liu4Jingyuan Huang5Bin Zhang6Jiawei Shen7Jiangang Cao8Department of Sports injury and Arthroscopy, Tianjin University Tianjin Hospital, Tianjin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Dermatology and cosmetology, Minhang Hospital, Fudan University, Shanghai, ChinaDepartment of Hand Surgery, Huashan Hospital, Fudan University, Shanghai, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Sports injury and Arthroscopy, Tianjin University Tianjin Hospital, Tianjin, ChinaIntroductionAlthough biomaterials strategies have been regarded as a promising approach for the treatment of osteoarthritis (OA), identifying novel drugs to be delivered for modulate macrophage polarization is still unclear. As a commonly used non-steroidal anti-inflammatory drug for OA, Imrecoxib may be a novel drug to direct and sustain macrophage phenotype. However, the specific protective mechanism of Imrecoxib in OA remains unclear. This study aims to investigate whether Imrecoxib would treat OA by regulating synovial macrophage polarization.MethodsThe research involves constructing mouse destabilization of medial meniscus (DMM) model to assess the changes in pain, bone destruction, cartilage degeneration, and synovial macrophage phenotypes following Imrecoxib treatment. Additionally, the effects of macrophage conditioned medium (CM) pretreated with Imrecoxib on the chondrocyte apoptosis, inflammation and degeneration-related factor expression were evaluated. The role of COX-2/PGE2 signaling pathway in the macrophage phenotype changes was further investigated.ResultsWe found that Imrecoxib alleviated pain, cartilage degeneration and synovitis, promoted polarization of M1 macrophages toward M2 phenotype in vivo and in vitro. In vitro experiments, Imrecoxib-CM protected chondrocyte by modulating macrophage polarization. Furthermore, Imrecoxib regulates macrophage polarization through the COX-2/PGE2 pathway.ConclusionThis study unravels that Imrecoxib protects joint cartilage and attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway, providing new drug delivery strategy for the clinical treatment of OA.https://www.frontiersin.org/articles/10.3389/fbioe.2025.1526092/fullosteoarthritisimrecoxibmacrophage polarizationcartilage protectionCOX 2/PGE2 |
| spellingShingle | Peng Peng Peng Peng Peng Peng Wanling Zheng Yuchen Liu Jingyuan Huang Bin Zhang Jiawei Shen Jiangang Cao Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway Frontiers in Bioengineering and Biotechnology osteoarthritis imrecoxib macrophage polarization cartilage protection COX 2/PGE2 |
| title | Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway |
| title_full | Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway |
| title_fullStr | Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway |
| title_full_unstemmed | Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway |
| title_short | Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway |
| title_sort | imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating cox 2 pge2 signaling pathway |
| topic | osteoarthritis imrecoxib macrophage polarization cartilage protection COX 2/PGE2 |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1526092/full |
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