Mechanism of Quanduzhong Capsules in treating knee osteoarthritis from perspective of spatial heterogeneity.
10.19540/j.cnki.cjcmm.20241211.401
- Author:
Zhao-Chen MA
1
;
Zi-Qing XIAO
2
;
Chu ZHANG
3
;
Yu-Dong LIU
1
;
Ming-Zhu XU
2
;
Xiao-Feng LI
4
;
Zhi-Ping WU
4
;
Wei-Jie LI
1
;
Yi-Xin YANG
3
;
Na LIN
1
;
Yan-Qiong ZHANG
1
Author Information
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
2. College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine Kunming 650500, China.
3. College of Pharmacy, Fujian University of Traditional Chinese Medicine Fuzhou 350122, China.
4. Jiangxi Puzheng Pharmaceutical Co., Ltd. Ji'an 331409, China.
- Publication Type:Journal Article
- Keywords:
Quanduzhong Capsules;
TXNIP-NLRP3-BMPR2-FN1-MMP2 signal axis;
knee osteoarthritis;
network proximity;
spatial transcriptomics
- MeSH:
Animals;
Osteoarthritis, Knee/metabolism*;
Drugs, Chinese Herbal/administration & dosage*;
Rats, Sprague-Dawley;
Rats;
Male;
Humans;
Capsules;
Female;
Disease Models, Animal
- From:
China Journal of Chinese Materia Medica
2025;50(8):2209-2216
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
