Potential involvement of connective tissue growth factor in chondrocytes apoptosis of Kashin-Beck disease

Xuena Yang; Huan Liu; Shiqiang Cheng; Chuyu Pan; Qingqing Cai; Xiaoge Chu; Sirong Shi; Wenming Wei; Dan He; Bolun Cheng; Yan Wen; Yumeng Jia; Alexey A. Tinkov; Anatoly V. Skalny; Feng Zhang

Ecotoxicology and Environmental Safety (Oct 2024)

Potential involvement of connective tissue growth factor in chondrocytes apoptosis of Kashin-Beck disease

Xuena Yang,
Huan Liu,
Shiqiang Cheng,
Chuyu Pan,
Qingqing Cai,
Xiaoge Chu,
Sirong Shi,
Wenming Wei,
Dan He,
Bolun Cheng,
Yan Wen,
Yumeng Jia,
Alexey A. Tinkov,
Anatoly V. Skalny,
Feng Zhang

Affiliations

Xuena Yang: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Huan Liu: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Shiqiang Cheng: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Chuyu Pan: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Qingqing Cai: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Xiaoge Chu: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Sirong Shi: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Wenming Wei: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Dan He: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Bolun Cheng: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yan Wen: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yumeng Jia: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Alexey A. Tinkov: Center of Bioelementology and Human Ecology, IM Sechenov First Moscow State Medical University (Sechenov University), Bolshaya Pirogovskaya St., 2-4, Moscow 119146, Russia; Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, Sovetskaya Str. 14, Yaroslavl 150000, Russia
Anatoly V. Skalny: Center of Bioelementology and Human Ecology, IM Sechenov First Moscow State Medical University (Sechenov University), Bolshaya Pirogovskaya St., 2-4, Moscow 119146, Russia; Peoples’ Friendship University of Russia (RUDN University), Moscow, Russia
Feng Zhang: Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China; Correspondence to: Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China. School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an 710061, China.

Journal volume & issue: Vol. 285
p. 117148

Abstract

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Background: Kashin-Beck disease (KBD) is an endemic osteoarthropathy characterized by excessive chondrocytes apoptosis. T-2 toxin exposure has been proved to be its etiology. Connective tissue growth factor (CTGF) exerts a profound influence on cartilage growth and metabolism. We investigated the potential role of CTGF in KBD development and examined CTGF alterations under T-2 toxin stimulation. Methods: The levels of CTGF and chondrocyte apoptosis-related markers in cartilage and primary chondrocytes from KBD and control groups were measured using qRT-PCR, Western blotting, immunohistochemistry, and immunofluorescence. We analyzed expression changes of these genes in response to T-2 toxin. Apoptosis rates of chondrocytes induced by T-2 toxin were measured by flow cytometry and TUNEL assay. The active pharmaceutical ingredient targeting CTGF was screened through Comparative Toxicogenomics Database, and molecular docking was performed using AutoDock Tools. Results: The CTGF levels in KBD cartilage and chondrocytes were significantly elevated and positively associated with the levels of apoptosis-related genes. T-2 toxin exposure increased CTGF and apoptosis-related gene levels in chondrocytes, with apoptosis rates rising alongside T-2 toxin concentration. Curcumin was identified as targeting CTGF and exhibited effective binding. It could down-regulate CTGF, apoptosis-related genes, such as Cleaved caspase 3 and BAX, and also significantly reduce apoptosis rate in chondrocytes treated with T-2 toxin. Conclusion: CTGF plays a crucial role in the development of KBD. Curcumin has shown potential in inhibiting CTGF levels and reducing chondrocyte apoptosis, highlighting its promise as a therapeutic agent for preventing cartilage damage in KBD. Our findings provided valuable insights into the pathogenesis of KBD and could promote the development of novel therapeutic strategies for this debilitating disease.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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