Platelet-rich plasma relieves inflammation and pain by regulating M1/M2 macrophage polarization in knee osteoarthritis rats
Abstract Knee osteoarthritis (KOA) is a common, chronic, degenerative disease. Platelet-rich plasma (PRP) can significantly relieve KOA pain; however, the mechanism of PRP-induced analgesia remains to be studied. Macrophages are closely related to KOA pain, and regulating macrophage polarization may...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-97501-6 |
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| author | Jiawei Xu Xiuping Chen Haina Zhang Xiyue Zhang Rujuan Liu Xin Li Junwei Wang Tieshan Li |
| author_facet | Jiawei Xu Xiuping Chen Haina Zhang Xiyue Zhang Rujuan Liu Xin Li Junwei Wang Tieshan Li |
| author_sort | Jiawei Xu |
| collection | DOAJ |
| description | Abstract Knee osteoarthritis (KOA) is a common, chronic, degenerative disease. Platelet-rich plasma (PRP) can significantly relieve KOA pain; however, the mechanism of PRP-induced analgesia remains to be studied. Macrophages are closely related to KOA pain, and regulating macrophage polarization may be an effective way to relieve KOA pain. Therefore, the aim of this study is: First, to explore whether PRP can effectively relieve pain in a KOA animal model and whether it relieves pain by regulating macrophage polarization. Second, to explore the mechanism by which PRP regulates macrophage polarization. Thirty-six healthy male SD rats were randomly divided into sham group, MIA group and PRP group. The KOA rat model was established by injecting 1 mg of MIA into the joint cavity. Behavioral tests, including weight-bearing asymmetry, hot plate, and von Frey hairs tests, were performed. The positive expression rates of inducible nitric oxide synthase (iNOS) and CD163 in the synovium were detected via immunohistochemical staining. Meanwhile, RAW 264.7 cells induced by lipopolysaccharide were treated with PRP in vitro. The production levels of the nuclear factor kappa-B (NF-κB) pathway-related proteins NF-κB p65, inhibitor-κ binding protein α (IκBα), p-NF-κB p65, p-IκBα and the iNOS and CD163 proteins were measured via western blotting. An enzyme-linked immunosorbent assay was used to detect the release of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), and nerve growth factor (NGF). The behavioral results revealed that PRP relieved pain. PRP reduced the proportion of M1/M2 macrophages among synovial macrophages, significantly inhibited the secretion of TNF-α and IL-1β in the synovium, and increased the secretion of IL-10. In addition, in vivo experiments revealed that PRP decreased the protein expression of iNOS, p-IκBα/IκBα, and p-p65/p65 and increased the protein expression of CD163. Furthermore, PRP decreased TNF-α, IL-1β, and NGF levels in RAW 264.7 cells and increased the secretion of IL-10. Our findings indicate that PRP can improve long-term relief from KOA pain. The analgesic mechanism promotes the transformation of M1 macrophages to M2 macrophages by inhibiting the NF-κB signaling pathway, which reduces the release of downstream pain-causing factors, thus relieving inflammation and pain. |
| format | Article |
| id | doaj-art-e9bc4e5818214be8bb437b3b74a51ee3 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-e9bc4e5818214be8bb437b3b74a51ee32025-08-20T03:18:22ZengNature PortfolioScientific Reports2045-23222025-04-0115111110.1038/s41598-025-97501-6Platelet-rich plasma relieves inflammation and pain by regulating M1/M2 macrophage polarization in knee osteoarthritis ratsJiawei Xu0Xiuping Chen1Haina Zhang2Xiyue Zhang3Rujuan Liu4Xin Li5Junwei Wang6Tieshan Li7Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao UniversityDepartment of Rehabilitation Medicine, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityThe First Affiliated Hospital of Xinxiang Medical UniversityChina Animal Health and Epidemiology CenterDepartment of Rehabilitation Medicine, The Affiliated Hospital of Qingdao UniversityChina Animal Health and Epidemiology CenterChina Animal Health and Epidemiology CenterDepartment of Rehabilitation Medicine, The Affiliated Hospital of Qingdao UniversityAbstract Knee osteoarthritis (KOA) is a common, chronic, degenerative disease. Platelet-rich plasma (PRP) can significantly relieve KOA pain; however, the mechanism of PRP-induced analgesia remains to be studied. Macrophages are closely related to KOA pain, and regulating macrophage polarization may be an effective way to relieve KOA pain. Therefore, the aim of this study is: First, to explore whether PRP can effectively relieve pain in a KOA animal model and whether it relieves pain by regulating macrophage polarization. Second, to explore the mechanism by which PRP regulates macrophage polarization. Thirty-six healthy male SD rats were randomly divided into sham group, MIA group and PRP group. The KOA rat model was established by injecting 1 mg of MIA into the joint cavity. Behavioral tests, including weight-bearing asymmetry, hot plate, and von Frey hairs tests, were performed. The positive expression rates of inducible nitric oxide synthase (iNOS) and CD163 in the synovium were detected via immunohistochemical staining. Meanwhile, RAW 264.7 cells induced by lipopolysaccharide were treated with PRP in vitro. The production levels of the nuclear factor kappa-B (NF-κB) pathway-related proteins NF-κB p65, inhibitor-κ binding protein α (IκBα), p-NF-κB p65, p-IκBα and the iNOS and CD163 proteins were measured via western blotting. An enzyme-linked immunosorbent assay was used to detect the release of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), and nerve growth factor (NGF). The behavioral results revealed that PRP relieved pain. PRP reduced the proportion of M1/M2 macrophages among synovial macrophages, significantly inhibited the secretion of TNF-α and IL-1β in the synovium, and increased the secretion of IL-10. In addition, in vivo experiments revealed that PRP decreased the protein expression of iNOS, p-IκBα/IκBα, and p-p65/p65 and increased the protein expression of CD163. Furthermore, PRP decreased TNF-α, IL-1β, and NGF levels in RAW 264.7 cells and increased the secretion of IL-10. Our findings indicate that PRP can improve long-term relief from KOA pain. The analgesic mechanism promotes the transformation of M1 macrophages to M2 macrophages by inhibiting the NF-κB signaling pathway, which reduces the release of downstream pain-causing factors, thus relieving inflammation and pain.https://doi.org/10.1038/s41598-025-97501-6Platelet-rich plasmaKnee osteoarthritisMacrophagesPainNF-κB |
| spellingShingle | Jiawei Xu Xiuping Chen Haina Zhang Xiyue Zhang Rujuan Liu Xin Li Junwei Wang Tieshan Li Platelet-rich plasma relieves inflammation and pain by regulating M1/M2 macrophage polarization in knee osteoarthritis rats Scientific Reports Platelet-rich plasma Knee osteoarthritis Macrophages Pain NF-κB |
| title | Platelet-rich plasma relieves inflammation and pain by regulating M1/M2 macrophage polarization in knee osteoarthritis rats |
| title_full | Platelet-rich plasma relieves inflammation and pain by regulating M1/M2 macrophage polarization in knee osteoarthritis rats |
| title_fullStr | Platelet-rich plasma relieves inflammation and pain by regulating M1/M2 macrophage polarization in knee osteoarthritis rats |
| title_full_unstemmed | Platelet-rich plasma relieves inflammation and pain by regulating M1/M2 macrophage polarization in knee osteoarthritis rats |
| title_short | Platelet-rich plasma relieves inflammation and pain by regulating M1/M2 macrophage polarization in knee osteoarthritis rats |
| title_sort | platelet rich plasma relieves inflammation and pain by regulating m1 m2 macrophage polarization in knee osteoarthritis rats |
| topic | Platelet-rich plasma Knee osteoarthritis Macrophages Pain NF-κB |
| url | https://doi.org/10.1038/s41598-025-97501-6 |
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