Mechanism of Tougu Xiaotong Capsules in alleviating glycolytic metabolism disorder of chondrocytes in osteoarthritis by modulating circFOXO3.
10.19540/j.cnki.cjcmm.20250409.708
- Author:
Chang-Long FU
1
;
Yan LUO
1
;
Jia-Jia XU
1
;
Yan-Ming LIN
1
;
Qing LIN
2
;
Yan-Feng HUANG
2
Author Information
1. College of Integrative Medicine, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine Fuzhou 350122, China Fujian Key Laboratory of Integrative Medicine on Geriatrics Fuzhou 350122, China.
2. College of Orthopaedic, Fujian University of Traditional Chinese Medicine Fuzhou 350122, China.
- Publication Type:Journal Article
- Keywords:
Tougu Xiaotong Capsules;
chondrocyte degeneration;
circFOXO3;
knee osteoarthritis
- MeSH:
Chondrocytes/metabolism*;
Animals;
Drugs, Chinese Herbal/administration & dosage*;
RNA, Circular/metabolism*;
Osteoarthritis/genetics*;
Glycolysis/drug effects*;
Humans;
Forkhead Box Protein O3/metabolism*;
Male;
Capsules;
Matrix Metalloproteinase 13/genetics*
- From:
China Journal of Chinese Materia Medica
2025;50(16):4641-4648
- CountryChina
- Language:Chinese
-
Abstract:
From the perspective of circular RNA forkhead box protein O3(circFOXO3) regulating glycolysis in osteoarthritis(OA) chondrocytes, this study investigated the mechanism by which Tougu Xiaotong Capsules(TGXTC) alleviated OA degeneration. In in vivo experiments, after randomized grouping and relevant interventions, morphological staining was used to observe structural changes in cartilage tissue. The mRNA level of circFOXO3 in cartilage tissue was detected by real-time quantitative PCR(RT-qPCR). Western blot analysis was used to detect changes in the expression of glucose transporter 1(GLUT1), hexokinase 2(HK2), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and matrix metalloproteinase 13(MMP13). In in vitro experiments, fluorescence in situ hybridization(FISH) was used to detect circFOXO3 expression in chondrocytes from each group. A lentiviral vector was used to construct circFOXO3-silenced(sh-circFOXO3) chondrocytes. RT-qPCR was used to analyze the changes in circFOXO3 levels after silencing, and Western blot was used to assess the regulatory effects of TGXTC on GLUT1, HK2, PKM2, LDHA, and MMP13 proteins in interleukin-1β(IL-1β)-induced chondrocytes under sh-circFOXO3 conditions. Masson staining and alcian blue staining results showed that the cartilage layer structure in the TGXTC and positive drug groups was improved compared with that in the model group. The mRNA level of circFOXO3 was significantly upregulated in both the TGXTC and positive drug groups, while the expression of the above-mentioned proteins was significantly reduced. FISH results showed that TGXTC upregulated the fluorescence intensity of circFOXO3 in IL-1β-induced chondrocytes. In the circFOXO3 silencing experiment, compared with the IL-1β group, circFOXO3 levels in the IL-1β + sh-circFOXO3 group were significantly decreased. Compared with the IL-1β + TGXTC group, circFOXO3 levels were significantly reduced in the IL-1β + sh-circFOXO3 + TGXTC group. Western blot results indicated that the elevated levels of GLUT1, HK2, PKM2, LDHA, and MMP13 proteins in chondrocytes of the IL-1β group were significantly inhibited by TGXTC intervention. However, this regulatory effect was attenuated after circFOXO3 silencing. In conclusion, TGXTC alleviate glycolytic metabolism disorder in OA chondrocytes and delay OA degeneration by regulating circFOXO3.
