General Information of the Disease (ID: DIS00120)
Name
Knee osteoarthritis
ICD
ICD-11: FA01
Full List of Target(s) of This Ferroptosis-centered Disease
Unspecific Target
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Responsed Disease Knee osteoarthritis [ICD-11: FA01]
Responsed Drug Stigmasterol Investigative
Responsed Regulator Sterol regulatory element-binding protein 2 Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model ATDC-5 cells Teratocarcinoma Mus musculus CVCL_3894
Response regulation Stigmasterol (STM) attenuates chondrocyte injury induced by IL-1 by regulating ferroptosis via down-regulation of SREBF2, which suggests that STM may have potential as a novel therapeutic method for knee osteoarthritis.
Transferrin receptor protein 1 (TFRC)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Knee osteoarthritis [ICD-11: FA01]
Responsed Drug Biochanin A Investigative
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model hCDs (Chondrocytes)
In Vivo Model
Male mice were purchased from Guangzhou University of Chinese Medicine's Experimental Animal Center C57BL/6 mice (7-week-old, 20 g) (Guangzhou, China). After one week of adaptively feeding with chow meals and sterilized water, the animals were separated into five groups of ten mice randomly assigned to the negative control (NC); model, positive control (PC); model group; high dosage of BCA treatment (BCA-H) group; and low dosage of BCA treatment (BCA-L) group. The iron overload mice model was designed based on earlier research. Except for the NC group, mice were administered ID intraperitoneally (500 mg/kg) once a week for eight weeks. In the right knee joints, OA was induced with the initial injection of iron dextran two weeks after the injection by destabilizing the medial meniscus (DMM) using a microscope. After the operation, the positive control group was administered with NAC intragastrically (100 mg/kg) for eight weeks. BCA-H and BCA-L groups were administered 20 mg/kg and 40 mg/kg of BCA separately for eight weeks according to previous studies.

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Response regulation Biochanin A (BCA) could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for knee osteoarthritis.
Solute carrier family 40 member 1 (SLC40A1)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Knee osteoarthritis [ICD-11: FA01]
Responsed Drug Biochanin A Investigative
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model hCDs (Chondrocytes)
In Vivo Model
Male mice were purchased from Guangzhou University of Chinese Medicine's Experimental Animal Center C57BL/6 mice (7-week-old, 20 g) (Guangzhou, China). After one week of adaptively feeding with chow meals and sterilized water, the animals were separated into five groups of ten mice randomly assigned to the negative control (NC); model, positive control (PC); model group; high dosage of BCA treatment (BCA-H) group; and low dosage of BCA treatment (BCA-L) group. The iron overload mice model was designed based on earlier research. Except for the NC group, mice were administered ID intraperitoneally (500 mg/kg) once a week for eight weeks. In the right knee joints, OA was induced with the initial injection of iron dextran two weeks after the injection by destabilizing the medial meniscus (DMM) using a microscope. After the operation, the positive control group was administered with NAC intragastrically (100 mg/kg) for eight weeks. BCA-H and BCA-L groups were administered 20 mg/kg and 40 mg/kg of BCA separately for eight weeks according to previous studies.

    Click to Show/Hide
Response regulation Biochanin A (BCA) could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for knee osteoarthritis.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Knee osteoarthritis [ICD-11: FA01]
Responsed Drug Biochanin A Investigative
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model hCDs (Chondrocytes)
In Vivo Model
Male mice were purchased from Guangzhou University of Chinese Medicine's Experimental Animal Center C57BL/6 mice (7-week-old, 20 g) (Guangzhou, China). After one week of adaptively feeding with chow meals and sterilized water, the animals were separated into five groups of ten mice randomly assigned to the negative control (NC); model, positive control (PC); model group; high dosage of BCA treatment (BCA-H) group; and low dosage of BCA treatment (BCA-L) group. The iron overload mice model was designed based on earlier research. Except for the NC group, mice were administered ID intraperitoneally (500 mg/kg) once a week for eight weeks. In the right knee joints, OA was induced with the initial injection of iron dextran two weeks after the injection by destabilizing the medial meniscus (DMM) using a microscope. After the operation, the positive control group was administered with NAC intragastrically (100 mg/kg) for eight weeks. BCA-H and BCA-L groups were administered 20 mg/kg and 40 mg/kg of BCA separately for eight weeks according to previous studies.

    Click to Show/Hide
Response regulation Biochanin A (BCA) could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for knee osteoarthritis.
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Knee osteoarthritis [ICD-11: FA01]
Responsed Drug Biochanin A Investigative
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model hCDs (Chondrocytes)
In Vivo Model
Male mice were purchased from Guangzhou University of Chinese Medicine's Experimental Animal Center C57BL/6 mice (7-week-old, 20 g) (Guangzhou, China). After one week of adaptively feeding with chow meals and sterilized water, the animals were separated into five groups of ten mice randomly assigned to the negative control (NC); model, positive control (PC); model group; high dosage of BCA treatment (BCA-H) group; and low dosage of BCA treatment (BCA-L) group. The iron overload mice model was designed based on earlier research. Except for the NC group, mice were administered ID intraperitoneally (500 mg/kg) once a week for eight weeks. In the right knee joints, OA was induced with the initial injection of iron dextran two weeks after the injection by destabilizing the medial meniscus (DMM) using a microscope. After the operation, the positive control group was administered with NAC intragastrically (100 mg/kg) for eight weeks. BCA-H and BCA-L groups were administered 20 mg/kg and 40 mg/kg of BCA separately for eight weeks according to previous studies.

    Click to Show/Hide
Response regulation Biochanin A (BCA) could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for knee osteoarthritis.
References
Ref 1 Stigmasterol alleviates interleukin-1beta-induced chondrocyte injury by down-regulatingsterol regulatory element binding transcription factor 2 to regulateferroptosis. Bioengineered. 2021 Dec;12(2):9332-9340. doi: 10.1080/21655979.2021.2000742.
Ref 2 Biochanin A protects against iron overload associated knee osteoarthritis via regulating iron levels and NRF2/System xc-/GPX4 axis. Biomed Pharmacother. 2023 Jan;157:113915. doi: 10.1016/j.biopha.2022.113915. Epub 2022 Nov 12.