Myricanone Alleviates Ferroptosis-related Osteoarthritis by Activating the ANXA5/Nrf2/HO-1 Pathway

doi:10.3870/j.issn.1672-0741.25.03.022

Abstract

Abstract: Objective To explore the mechanism of myricanone (Myri) in the treatment of osteoarthritis(OA). Methods ATDC5 cells were treated with different concentrations of Myri(0,25,50,100,150,200 μmol/L)for 48 h,and the cell viability was detected by MTT to screen the safe therapeutic concentration.ATDC5 cells stimulated with 100 ng/mL lipopolysaccharides(LPS)were used to induce cell inflammation for 24 h,and then ATDC5 cells were treated with 50 μmol/L Myri,2.0 μg/mL annexin A5(ANXA5) overexpression vector(pcDNA-ANXA5)and 50 nmol/L ANXA5 interference plasmid(si-ANXA5)alone or together.Cell viability and ferroptosis levels were detected by MTT and the corresponding commercial kits.The OA mouse model was constructed by cruciate ligament transection and medial meniscectomy for in vivo experiments. Results When the concentration of Myri was more than 100 μmol/L,the activity of ATDC5 cells was decreased.In addition,Myri improved LPS-induced ATDC5 cells viability reduction and inhibited ferroptosis.ANXA5 was lowly expressed in LPS-treated ATDC5 cells.Overexpression of ANXA5 attenuated LPS-induced decrease in ATDC5 cell viability and increase in ferroptosis by activating the Nrf2/HO-1 pathway.Interfering with ANXA5 offset the inhibitory effect of Myri on the level of ferroptosis in LPS-treated ATDC5 cells.In vivoexperiments further confirmed that Myri inhibited ferroptosis by promoting ANXA5 expression,thereby improving OA. Conclusion Myri inhibits ferroptosis and alleviates OA by activating the ANXA5/Nrf2/HO-1 pathway,which may have potential value for the treatment of OA.

Key words: osteoarthritis, myricanone, annexin A5, Nrf2/HO-1 pathway, ferroptosis

CLC Number:

R684.3
R285

Ma Yunfeng, Han Xiaofei. Myricanone Alleviates Ferroptosis-related Osteoarthritis by Activating the ANXA5/Nrf2/HO-1 Pathway[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(3): 370-377.

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