Fraxetin Inhibits Ferroptosis and Alleviates Cartilage Damage in Osteoarthritis Rat Through Nrf2/HO-1 Signaling Pathway

doi:10.12300/j.issn.1674-5817.2026.033

Abstract

Abstract:

Objective To explore whether fraxetin can alleviate cartilage injury and its potential mechanism in rats with ACLT-induced osteoarthritis. Methods Eighteen SD rats were randomly divided into three groups: the sham operation (Sham) group, the model (ACLT) group, and the fraxetin intervention (ACLT+Fra) group; Except for the Sham group, OA rat models were established by ACLT method in the other two groups; One week after surgery, the ACLT+Fra group was injected with fraxetin (5 mg/kg/day) into the knee joint, twice a week for 4 consecutive weeks; H&E staining and safranin O-fast green staining were used to observe the knee joint cartilage injury in each group; The Mankin scoring system and the OARSI scoring system were adopted to evaluate the degree of knee joint damage; Immunohistochemical staining was used to detect the expression of MMP13, Col2, GPX4, and HO-1 in the knee joint cartilage of each group; The WB was used to detect the protein expression levels of MMP13, Col2, Nrf2, HO-1, SLC7A11, and GPX4 in rat cartilage; qRT-PCR was used to detect the mRNA expression levels of MMP13, Col2, Nrf2, HO-1, SLC7A11, and GPX4; Kits were used to detect the differences in the contents of GSH, MDA, and Fe2? in the knee joint cartilage of rats in each group. Results Compared with the Sham group, the ACLT group rats showed severe cartilage surface damage, degradation of the cartilage matrix, and significantly reduced Mankin and OARSI scores(P<0.01); immunohistochemistry results showed a significant increase in MMP13 positive expression (P<0.01), and a significant decrease in Col2, GPX4, and HO-1 positive expression(P<0.01); MDA and Fe2? contents were significantly increased(P<0.01), while GSH levels were significantly decreased(P<0.01); MMP13 protein and mRNA expressions were significantly elevated(P<0.01), and Col2, Nrf2, HO-1, SLC7A11, and GPX4 protein and mRNA expressions were significantly decreased(P<0.01).Compared with the ACLT group, the ACLT+Fra group rats showed reduced cartilage surface damage, with significantly increased Mankin and OARSI scores(P<0.01); immunohistochemical results showed a significant decrease in MMP13 positive expression(P<0.05), and a significant increase in Col2, GPX4, and HO-1 positive expression(P<0.01); MDA and Fe2? contents were significantly reduced(P<0.01), and GSH levels were significantly increased(P<0.05); MMP13 protein and mRNA expressions were significantly decreased(P<0.01), and Col2, Nrf2, HO-1, SLC7A11, and GPX4 protein and mRNA expressions were significantly increased(P<0.05). Conclusion Fraxetin may exert a cartilage protective effect by activating the Nrf2/HO-1 signaling pathway to inhibit chondrocyte ferroptosis.

Key words: Fraxetin, Osteoarthritis, Cartilage, Ferroptosis, Rats

CLC Number:

Q95-33

YANG Ran,FENG Jiwei,MA Fei,et al. Fraxetin Inhibits Ferroptosis and Alleviates Cartilage Damage in Osteoarthritis Rat Through Nrf2/HO-1 Signaling Pathway[J]. Laboratory Animal and Comparative Medicine. DOI: 10.12300/j.issn.1674-5817.2026.033.

Figures/Tables 7

References 28

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基因 Gene	正向引物 Forward primer	反向引物 Reverse primer
MMP13	CTTCTTCTTGTTGAGCTGGACTC	CTGTGGAGGTCACTGTAGACT
Col2	GGGAATGTCCTCTGCGATGAC	GAAGGGGATCTCGGGGTTG
Nrf2	TCTTGGAGTAAGTCGAGAAGTGT	GTTGAAACTGAGCGAAAAAGGC
HO-1	AAGCCGAGAATGCTGAGTTCA	GCCGTGTAGATATGGTACAAGGA
SLC7A11	GGCACCGTCATCGGATCAG	CTCCACAGGCAGACCAGAAAA
GPX4	GATGGAGCCCATTCCTGAACC	CCCTGTACTTATCCAGGCAGA
β-actin	GGCTGTATTCCCCTCCATCG	CCAGTTGGTAACAATGCCATGT

基因 Gene	正向引物 Forward primer	反向引物 Reverse primer
MMP13	CTTCTTCTTGTTGAGCTGGACTC	CTGTGGAGGTCACTGTAGACT
Col2	GGGAATGTCCTCTGCGATGAC	GAAGGGGATCTCGGGGTTG
Nrf2	TCTTGGAGTAAGTCGAGAAGTGT	GTTGAAACTGAGCGAAAAAGGC
HO-1	AAGCCGAGAATGCTGAGTTCA	GCCGTGTAGATATGGTACAAGGA
SLC7A11	GGCACCGTCATCGGATCAG	CTCCACAGGCAGACCAGAAAA
GPX4	GATGGAGCCCATTCCTGAACC	CCCTGTACTTATCCAGGCAGA
β-actin	GGCTGTATTCCCCTCCATCG	CCAGTTGGTAACAATGCCATGT