Work

The role of AKR1C3 in regulating chondrocyte aging in knee osteoarthritis

Year: 2026

Type: article

Abstract: Background Osteoarthritis is a common joint disease characterized by the aging and death of cartilage cells, accompanied by inflammation. This study aimed to systematically evaluate the regulatory Impacts of aldo-keto reductase family 1 member C3 (AKR1C3) on chondrocyte senescence, apoptosis, inflammation, and extracellular matrix metabolism, and to explore its potential for clinical translation. Methods In this study, a chondrocyte senescence model was established using tert-butyl hydroperoxide (TBHP), with 100 μM TBHP treatment for 48 h identified as the optimal induction condition. AKR1C3 expression was detected by qPCR and Western blot, and the effects of its silencing on apoptosis, SA-β-gal activity, inflammatory factors, γH2AX, MMP3, and COL2A1 were evaluated. Downstream targets were screened via transcriptomic analysis, and the role of CYP2J2 in the p-p53/p21 pathway was validated through interference experiments. In vivo validation was performed in an ACLT-induced rat knee osteoarthritis model via intra-articular injection of AKR1C3-shRNA adenovirus. Results Silencing AKR1C3 markedly attenuated apoptosis, SA-β-gal activity, inflammatory cytokines, γH2AX, and MMP3 while enhancing COL2A1 in senescent chondrocytes. Transcriptomic analysis revealed that 139 genes were upregulated and 12 genes were downregulated after silencing, Especially, the upregulation of CYP2J2 is particularly significant CYP2J2 interference partially counteracted the anti-senescent effects of AKR1C3 knockdown via the p-p53/p21 axis. In ACLT-induced KOA rats, AKR1C3-shRNA improved cartilage thickness, lowered apoptosis and inflammation, downregulated γH2AX, p-p53, p21, and MMP3, and restored CYP2J2 and COL2A1. Conclusions Our findings underscore the pivotal role of AKR1C3 in chondrocyte senescence and apoptosis, mediated via the CYP2J2-p-p53/p21 axis, positioning it as a promising therapeutic target for osteoarthritis.

Source: Journal of Radiation Research and Applied Sciences

DOI: 10.1016/j.jrras.2026.102272

Authors: Dongxu Chen, Dachao Huang, Xueqiao Chen, Qiufang Deng, Kang Tian, Weiguo Zhang

Institutions: Guilin Medical University, Dalian Medical University, First Affiliated Hospital of Dalian Medical University

Language: English

Topic: Osteoarthritis Treatment and Mechanisms

Subfield: Rheumatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,400