Exploration of signaling pathways with unclear action status and possible effects on related diseases or functions after knockdown of silencing information regulator 1 gene in chondrocytes

doi:10.12307/2024.352

Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (20): 3123-3129.doi: 10.12307/2024.352

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Exploration of signaling pathways with unclear action status and possible effects on related diseases or functions after knockdown of silencing information regulator 1 gene in chondrocytes

Ye Haiming1, 2, 3, Zeng Hui1, 2, 3, Yang Qi4, Zhang Geng1, 2, 3, Weng Jian1, 2, 3, Yu Fei1, 2, 3

1Department of Bone & Joint Surgery, 4Department of Medical Ultrasound, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China; 2National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Shenzhen 518036, Guangdong Province, China; 3Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Shenzhen 518036, Guangdong Province, China

Received:2023-05-04 Accepted:2023-06-15 Online:2024-07-18 Published:2023-09-09
Contact: Yu Fei, MD, Physician, Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China; National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Shenzhen 518036, Guangdong Province, China; Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Shenzhen 518036, Guangdong Province, China
About author:Ye Haiming, Associate chief physician, Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China; National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Shenzhen 518036, Guangdong Province, China; Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Shenzhen 518036, Guangdong Province, China
Supported by:
the National Natural Science Foundation of China, No. 82102568 (to YF); the Basic and Applied Basic Research Fund of Guangdong Province, Nos. 2021A1515012586 and 2022A1515220111 (both to YF); the Scientific Research Foundation of Peking University Shenzhen Hospital, No. KYQD2021099 (to YF); Shenzhen Project of Three Famous Items for Medical Care and Public Health, No. SZSM201612092 (to ZH); Shenzhen Medical Key Discipline Construction Fund, No. SZXK023 (to ZH); Shenzhen High-level Hospital Construction Special Fund (to ZH)

Abstract

Abstract: BACKGROUND: silencing information regulatory 1 (SIRT1) regulates the function of related proteins in chondrocytes in a deacetylated manner and participates in chondrocyte proliferation and differentiation, thereby promoting cartilage defect repair.
OBJECTIVE: To screen for signaling pathways with unclear action status after SIRT1 gene knockdown in chondrocytes, as well as diseases or functions that produce changes using high-throughput technology.
METHODS: ATDC5 chondrocytes from mice in logarithmic growth phase were divided into two groups: the cells were transfected with SIRT1 gene knockdown negative control lentivirus in control group and SIRT1 gene knockdown lentivirus in experimental group. GeneChip® Mouse Genome 430 2.0 Array was used to detect the mRNA expression at 72 hours after transfection. Applied bioinformatics technology was also used to screen for unclear activation or inhibition signaling pathways and their related factors. Moreover, enrichment of disease or function modules was analyzed.
RESULTS AND CONCLUSION: After knocking down the SIRT1 gene, there were 245 signaling pathways with unclear activation or inhibition status in the mouse ATDC5 chondrocytes. According to the ranking of -Log (P-value), we reported the factors in the top 20 signaling pathways with unclear activation or inhibition status, including IGFBP4, TGFBR1, CTGF, COL4A5, LHX2, IL1RL1, and KLF6. According to the ranking of -Log (P-value), there were significant changes in 14 disease or function modules, including cellular growth and proliferation, organism survival, cell death and survival. According to the number of differentially expressed genes, there were significant changes in three disease or function modules, including organismal injury and abnormalities, cancer, and cell death and survival. According to the comprehensive ranking of -Log (P-value) and the number of differentially expressed genes, the disease or function module related to intrinsic immune response was significantly activated.

Key words: high throughput technology, silent information regulator 1, cartilage defect, signaling pathway, disease or function

CLC Number:

Ye Haiming, Zeng Hui, Yang Qi, Zhang Geng, Weng Jian, Yu Fei. Exploration of signaling pathways with unclear action status and possible effects on related diseases or functions after knockdown of silencing information regulator 1 gene in chondrocytes[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(20): 3123-3129.

Figures/Tables 6

References

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Exploration of signaling pathways with unclear action status and possible effects on related diseases or functions after knockdown of silencing information regulator 1 gene in chondrocytes

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