Apigenin Inhibits the Progression of Osteoarthritis by Mediating Macrophage Polarization

Abstract

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.

Reprogramming Macrophage Polarization, Depleting ROS by Astaxanthin and Thioketal‐Containing Polymers Delivering Rapamycin for Osteoarthritis Treatment

“…IL‐1β and IL‐6 are crucial inflammatory mediators released by M1 macrophages and are involved in the degeneration of joint cartilage. [ 25 ] To investigate whether NP@Poly RHAPM might restrict the release of inflammatory mediators in M1 macrophages, the levels of IL‐1β and IL‐6 in cell supernatants were measured using an enzyme‐linked immunosorbent assay (ELISA). The results demonstrated that IL‐1β and IL‐6 were significantly generated by M1 macrophages.…”

Anti-inflammation is an important way that Qingre-Huazhuo-Jiangsuan recipe treats acute gouty arthritis

“…There is research that found that cis-resveratrol could reduce inflammation by inhibiting canonical and non-canonical inflammasomes in macrophages ( Huang et al, 2014 ). Apigenin alleviates macrophage-polarization-induced inflammatory response ( Ji et al, 2023 ). Apigenin has been shown to exert anti-inflammatory activity ( Ouyang et al, 2021 ).…”

Gentiopicroside ameliorates the lipopolysaccharide-induced inflammatory response and hypertrophy in chondrocytes

“…Cells in each group were collected, total RNA was extracted by an RNA isolation and extraction kit, the RNA was reverse transcribed into cDNA by a reverse transcription kit, the housekeeping gene GAPDH was selected as an internal reference, and real-time fluorescence quantitative PCR was performed by using SYBR® GreenERTM SuperMix Universal (Invitrogen®) [ 30 ]. Relative expression was calculated by the 2-ΔΔCt method (ΔCt is the difference between the threshold cycle of the samples and the reference value of GAPDH), and the sequences of the primers used in the experiment are listed in Table 1 .…”