Mathematical modeling and application of IL-1β/TNF signaling pathway in regulating chondrocyte apoptosis

Yishu Wang; Jingxiang Liu; Boyan Huang; Xiaojun Long; Xiuyun Su; Deshun Sun

doi:10.3389/fcell.2023.1288431

Mathematical modeling and application of IL-1β/TNF signaling pathway in regulating chondrocyte apoptosis

Front Cell Dev Biol. 2023 Nov 2:11:1288431. doi: 10.3389/fcell.2023.1288431. eCollection 2023.

Authors

Yishu Wang^#¹, Jingxiang Liu^#², Boyan Huang^#³, Xiaojun Long⁴, Xiuyun Su⁵, Deshun Sun^{5

6}

Affiliations

¹ Medical Research Center, Southern University of Science and Technology Hospital, Shenzhen, China.
² School of Marine Electrical Engineering, Dalian Maritime University, Dalian, China.
³ Department of Medical Oncology, Southern University of Science and Technology Hospital, Shenzhen, China.
⁴ Department of Colorectal Surgery, Key Laboratory of Biological Treatment of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
⁵ Intelligent Medical Innovation Institute, Southern University of Science and Technology Hospital, Shenzhen, China.
⁶ Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Laboratory of Digital Orthopedic Engineering, Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University, Health Science Center), Shenzhen, China.

^# Contributed equally.

Abstract

Introduction: Mathematical model can be used to model complex biological processes, and have shown potential in describing apoptosis in chondrocytes. Method: In order to investigate the regulatory mechanisms of TNF signaling pathway in regulating chondrocyte apoptosis, a fractional-order differential equation model is proposed to describe the dynamic behavior and mutual interaction of apoptosis-related genes under the activation of TNF signaling pathway. Compared with the traditional molecular biology techniques, the proposed mathematical modeling has advantages to providing a more comprehensive understanding of the regulatory mechanisms of TNF signaling pathway in chondrocyte apoptosis. Result: In this paper, differentially expressed genes induced by IL-1β in human chondrocyte apoptosis are screened using high-throughput sequencing. It is found that they were significantly enriched in the TNF signaling pathway. Therefore, a mathematical model of the TNF signaling pathway is built. Using real-time PCR experiments, mRNA data is measured and used to identify the model parameters, as well as the correlation coefficient. Finally, the sensitivity of the model parameters is discussed by using numerical simulation methods, which can be used to predict the effects of different interventions and explore the optimal intervention strategies for regulating chondrocyte apoptosis. Discussion: Therefore, fractional-order differential equation modeling plays an important role in understanding the regulatory mechanisms of TNF signaling pathway in chondrocyte apoptosis and its potential clinical applications.

Keywords: TNF signal pathway; chondrocyte apoptosis; mathematical model; parameter estimate; sensitive analysis.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. The work is supported by the National Natural Science Foundation of China (62103287), Guangdong Provincial Natural Science Foundation General Project (2023A1515010518), Basic Research General Project of Shenzhen (JCYJ20210324103209026), PhD Basic Research Initiation Project (RCBS20200714114856171, RCBS20200714114909099), Shenzhen Nanshan District Excellent Youth Fund Project (NSZD2023061), President's Fund of Southern University of Science and Technology Hospital (2022-A3) and Clinical Research Project of Shenzhen Second People’s Hospital (20213357007).