Abnormal expression of TSG-6 disturbs extracellular matrix homeostasis in chondrocytes from endemic osteoarthritis

Yujie Ning; Pan Zhang; Feiyu Zhang; Sijie Chen; Yanli Liu; Feihong Chen; Yifan Wu; Shujin Li; Chaowei Wang; Yi Gong; Minhan Hu; Ruitian Huang; Hongmou Zhao; Xiong Guo; Xi Wang; Lei Yang

doi:10.3389/fgene.2022.1064565

Abnormal expression of TSG-6 disturbs extracellular matrix homeostasis in chondrocytes from endemic osteoarthritis

Front Genet. 2022 Nov 18:13:1064565. doi: 10.3389/fgene.2022.1064565. eCollection 2022.

Authors

Yujie Ning¹, Pan Zhang², Feiyu Zhang¹, Sijie Chen¹, Yanli Liu¹, Feihong Chen¹, Yifan Wu¹, Shujin Li¹, Chaowei Wang¹, Yi Gong¹, Minhan Hu¹, Ruitian Huang¹, Hongmou Zhao³, Xiong Guo^{1

4}, Xi Wang¹, Lei Yang⁵

Affiliations

¹ Key Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Xi'an Jiaotong University Health Science Center, National Health Commission of the People's Republic of China, Xi'an, China.
² Sichuan Center for Disease Control and Prevention, Chengdu, China.
³ Foot and Ankle Surgery Department, Honghui Hospital of Xi'an Jiaotong University, Xi'an, China.
⁴ Clinical Research Center for Endemic Disease of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁵ School of Nursing, Health Science Center, Xi'an Jiaotong University, Xi'an, China.

Abstract

Background and aims: Kashin-Beck disease (KBD) is a unique endemic osteochondropathy with unclear pathogenesis in China. T-2 toxin exposure has been identified as a significant risk factor of KBD. However, the mechanism of articular cartilage damage induced by T-2 toxin is a conundrum. We explored the role of the extracellular matrix-related gene TSG-6 in the articular chondrocyte damage process under the exposure of HT-2 toxin. Methods: TSG-6 was identified as a candidate gene by mining our previous gene expression profiling of KBD and verified by qRT-PCR and immunohistochemistry. Then, TSG-6 was silenced by RNA interference technology and overexpressed induction by TNF-α. Gradient concentrations of HT-2 toxin were added to intervene with C28/I2 chondrocytes. MTT was used to observe the proliferation and cell viability of chondrocytes, and qRT-PCR was utilized to detect the expression changes of MMP1, MMP3, MMP13, COL2A1, and proteoglycan before and after treatments for verification. Results: TSG-6 was upregulated in KBD chondrocytes at the mRNA level and upregulated in the superficial, middle, and deep zones of KBD cartilage. After TSG-6 silencing, the expression of MMP1, MMP3, MMP13, and proteoglycan was significantly decreased while COL2A1 expression was significantly increased, which was reversed after the overexpression of TSG-6 induced by TNF-α (p < 0.05). The survival rate of chondrocytes was correspondingly reduced with an increase in the HT-2 toxin concentration. Compared with the blank control group, the expression of MMPs was increased in the intervention group of HT-2 toxin, while the expression of proteoglycan and COL2A1 decreased (p < 0.05). Conclusion: The upregulation of the TSG-6 gene may play a role in promoting the damage and degradation of the extracellular matrix in KBD chondrocytes under the exposure of HT-2 toxin.

Keywords: HT-2 toxin; Kashin-Beck disease; TSG-6; chondrocytes; extracellular matrix.