Apigenin Inhibits the Progression of Osteoarthritis by Mediating Macrophage Polarization
Xueyan Ji1, Wei Du2, Wenqing Che1
1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
Objective:
The overall purpose of this study was to investigate the mechanism of macrophage polarization on chondrocyte injury in osteoarthritis and the protective effect of apigenin on chondrocytes in osteoarthritis.
Method:
Primary chondrocytes were isolated from the knee cartilage of three-day-old mice, and cells positive for Alsine blue staining and type II collagen immunocytochemical staining were identified and used in followup experiments. Transwell coculture was performed. Chondrocytes were inoculated in the inferior compartment, and macrophages were inoculated in the upper compartment. The experimental groups were the N group, LPS group, and LPS+ apigenin group. The effect of macrophage polarization on chondrocyte inflammation and the protective effect of apigenin on chondrocytes were verified by the drug administration. Real-time quantitative PCR (qPCR) and Western blot were used to detect the expression of RNA and protein. Experimental OA was induced by modified Hulth surgery in mice. Modified Hulth surgery was performed on the mouse's right knee to induce experimental osteoarthritis in mice, with the nonoperative right knee serving as an ipsilateral control. The mice were randomly assigned to three groups (six mice per group): the sham group, the modified Hulth group, and the modified Hulth + apigenin group. Animals were given gavage for four weeks. The protective effect of apigenin on articular cartilage was verified by histological staining and immunohistochemical analysis.
Results:
Histological staining showed that apigenin had a protective effect on cartilage degeneration induced by modified Hulth surgery. The PCR results showed that apigenin significantly reduced the expression levels of IL-1, IL-6, MMP3, and MMP13 in the articular cartilage of OA mice, and it had a protective effect on articular cartilage. Apigenin reduced the levels of IL-1, IL-6, TNF-α, and IL-12 in macrophages and increased the levels of MG-L1, MG-L2, ARG-1, and IL-10, which can inhibit the M1 polarization of macrophages and promote M2 polarization. In the coculture system, apigenin decreased the protein levels of TRPM7, P-mTOR, BAX, and c-caspase3 in macrophages, while significantly increasing the protein levels of Bcl2. The levels of IL-1, IL-6, MMP13, TNF-α, P38, JNK, and ERK phosphorylation were reduced in chondrocytes.
Conclusion:
Apigenin alleviates cartilage injury in OA mice induced by modified Hulth. Apigenin inhibits chondrocyte inflammation through the MAPK pathway. Apigenin alleviates macrophage-polarization-induced inflammatory response and chondrocyte apoptosis in the macrophage-chondrocyte coculture system through the TRPM7-mTOR pathway.
Insights
Apigenin protects against osteoarthritis (OA) by reducing cartilage damage and inhibiting inflammation. It modulates macrophage polarization and alleviates chondrocyte apoptosis via the TRPM7-mTOR pathway.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Osteoarthritis (OA) is characterized by chondrocyte injury and inflammation.
- Macrophage polarization plays a critical role in OA pathogenesis.
- Apigenin is a natural compound with potential therapeutic properties.
Purpose of the Study:
- To investigate the mechanism of macrophage polarization in chondrocyte injury in OA.
- To evaluate the protective effect of apigenin on chondrocytes in OA.
Main Methods:
- Primary chondrocytes and macrophages were used in a Transwell co-culture system.
- Experimental OA was induced in mice using modified Hulth surgery.
- Apigenin's effects were assessed using qPCR, Western blot, histological staining, and immunohistochemical analysis.
Main Results:
- Apigenin demonstrated a protective effect on cartilage degeneration in OA mice.
- Apigenin reduced pro-inflammatory mediators (IL-1, IL-6, MMP3, MMP13) and modulated macrophage polarization (inhibited M1, promoted M2).
- Apigenin alleviated chondrocyte inflammation and apoptosis by affecting the TRPM7-mTOR and MAPK pathways.
Conclusions:
- Apigenin alleviates cartilage injury in OA by inhibiting chondrocyte inflammation via the MAPK pathway.
- Apigenin mitigates macrophage-polarization-induced inflammation and chondrocyte apoptosis through the TRPM7-mTOR pathway.
