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Updated: Jul 9, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Afzelin alleviates osteoarthritis by suppressing pyroptosis through decreasing NSUN5-mediated NLRC4 m5C modification
Hainan Hong1, Shuai He1, Jianqiang Huang2
1Orthopedic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China.
Objective:
Osteoarthritis (OA) is characterized by the destruction of chondrocytes, in which chondrocyte pyroptosis has been demonstrated to be a key mechanism driving OA progression. 5-Methylcytosine (m5C) modification has been implicated in various biological processes, yet its role in mediating OA remains poorly understood. Afzelin, a natural compound with potent anti-inflammatory properties, but its effects on OA remains uncertain. This study aimed to investigate the therapeutic effects and underlying mechanisms of afzelin in OA.
Methods:
C57BL/6 mice underwent a medial meniscotibial ligament transection to induce OA development. Human chondrocytes were stimulated by LPS to induce the OA in vitro model. Both OA in vivo and in vitro model received afzelin treatment. ELISA was performed to evaluate the inflammation in vivo and in vitro. Western blot was performed to detect the levels of pyroptosis-related proteins. The underlying mechanism was investigated by methylated RNA immunoprecipitation (MeRIP), RIP and dual luciferase report.
Results:
Results showed that afzelin suppressed inflammatory infiltration in the cartilage of OA mice and inhibited the inflammation in bone marrow-derived macrophages extracted from OA mice. Afzelin inhibited the inflammation, pyroptosis and NSUN5 expression in the in vitro OA model, while NSUN5 overexpression reversed these inhibition. Moreover, NSUN5 overexpression enhanced the stability of NLRC4 mRNA by increasing NLRC4 m5C modification. NLRC4 overexpression restored the inflammation and pyroptosis suppressed by NSUN5 knockdown in the in vitro OA model.
Conclusions:
These findings suggested that afzelin inhibited OA progression by suppressing pyroptosis through inhibiting NLRC4 expression by downregulating NSUN5. This study provided a new drug and potential target for the treatment of OA.
Insights
Afzelin, a natural compound, effectively treats osteoarthritis (OA) by reducing inflammation and pyroptosis. It targets NSUN5 and NLRC4, offering a new therapeutic avenue for OA.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Osteoarthritis (OA) is characterized by chondrocyte destruction, with pyroptosis being a key driver of its progression.
- The role of 5-methylcytosine (m5C) modification in OA pathogenesis is not well understood.
- Afzelin, a natural compound, possesses anti-inflammatory properties, but its therapeutic potential in OA requires investigation.
Purpose of the Study:
- To investigate the therapeutic effects of afzelin on osteoarthritis.
- To elucidate the underlying mechanisms of afzelin's action in OA, focusing on m5C modification and pyroptosis.
Main Methods:
- Osteoarthritis was induced in C57BL/6 mice and human chondrocytes.
- Afzelin treatment was administered to both in vivo and in vitro OA models.
- Inflammation, pyroptosis-related proteins, m5C modification, and mRNA stability were assessed using ELISA, Western blot, MeRIP, RIP, and dual-luciferase reporter assays.
Main Results:
- Afzelin suppressed inflammation and pyroptosis in OA models.
- Afzelin downregulated NSUN5 expression, which was reversed by NSUN5 overexpression.
- NSUN5 overexpression enhanced NLRC4 mRNA stability via m5C modification, and NLRC4 overexpression restored pyroptosis.
Conclusions:
- Afzelin inhibits OA progression by suppressing pyroptosis via downregulation of NSUN5 and subsequent inhibition of NLRC4 expression.
- Afzelin represents a potential therapeutic agent for OA treatment.
- Targeting the NSUN5-NLRC4 pathway offers a novel strategy for OA management.
