Activation of chondrocyte degeneration related signaling pathways and expression of differential factors in ATDC5 mouse cells after silent information regulator 1 knockdown

doi:10.12307/2022.849

Chinese Journal of Tissue Engineering Research ›› 2022, Vol. 26 ›› Issue (32): 5112-5118.doi: 10.12307/2022.849

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Activation of chondrocyte degeneration related signaling pathways and expression of differential factors in ATDC5 mouse cells after silent information regulator 1 knockdown

Xie Xiaochen1, 2, Yang Qi3, Weng Jian1, 2, Zeng Hui1, 2, Kang Bin1, 2, Liu Pei1, 2, Zhong Huage4, Yu Fei1, 2

1Department of Bone & Joint Surgery, 3Department 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; 4Department of Gastrointestinal Surgery, Guangxi Medical University Affiliated Tumor Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China

Received:2021-08-30 Accepted:2021-10-15 Online:2022-11-18 Published:2022-05-12
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
About author:Xie Xiaochen, 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
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 2019A1515110983 (both to YF); Bethune · CSPC Osteoporosis Scientific Research Fund Project, No. G-X-2020-1107-21 (to YF); the National Natural Science Foundation of China, No. 82102076 (to YQ); the National Natural Science Foundation of China, No. 82172432 (to ZH); Guangdong Basic and Applied Basic Research Fund, No. 2019A1515011290 (to ZH); the National Natural Science Foundation of China, No. 82001319 (to WJ)

Abstract

Abstract: BACKGROUND: Chondrocytes degeneration often leads to common orthopedic diseases such as osteoarthritis, intervertebral disc degeneration and meniscus degeneration. SIRT1 gene is closely related to chondrocytes degeneration. When SIRT1 gene is knocked down in ATDC5 mouse chondrocytes, it can affect cell function via signaling pathways related to chondrocyte degeneration, and then affect the process of orthopedic diseases.
OBJECTIVE: To investigate the significantly activated signaling pathways related to chondrocyte degeneration and the expression of differential factors in ATDC5 mouse chondrocytes after SIRT1 gene knockdown.
METHODS: The lentivirus carrying SIRT1 gene or not was transfected into ATDC cells. The transfected cells were divided into control (transfected with negative control lentivirus) and experiment group (transfected with lentivirus carrying SIRT1 gene). Total RNA was extracted for quality testing. Gene chip was used to detect the expression of coding RNA in the cells. Combined with bioinformatics analysis, we identified significantly activated signaling pathways related to chondrocyte degeneration, and elaborated differentially expressed factors in some signaling pathways.
RESULTS AND CONCLUSION: Forty-two signaling pathways were significantly activated in ATDC5 cells after SIRT1 gene knockdown. Among them, we selected five signaling pathways related to chondrocyte degeneration and reported less, including hepatocyte growth factor signaling pathway (ETS1, PIK3CA, NRAS, PIK3C2A, FGFR2, ELF1, FGFR3, CDKN1A, AKT3, FRS2, PRKD3, MAP3K2; Ratio=0.139 0, Z-score=2.673), neuregulin signaling pathway (RPS6KB1, STAT5A, MTOR, BTC, HBEGF, RNF41; Ratio=0.136 0, Z-score=2.309), insulin receptor signaling pathway (TSC1, EIF4EBP1, PRKAR2B, PPP1R12A, TSC2; Ratio=0.106 0, Z-score=2.138), chemokine receptor 4 signaling pathway (PAK4, EGR1, RHOJ, RHOB, PLCB1, GNG5; Ratio=0.097 0, Z-score=2.500), actin cytoskeleton signaling pathway (ABI2, BRK1, PIP4K2B, MYLK, IQGAP1, ARPC1A, ACTA2, EZR, SSH2, ACTG1, IQGAP3; Ratio=0.092 1, Z-score=2.236), so as to provide novel targets for treating chondrocyte degeneration related diseases.

Key words: SIRT1, ATDC5 cell, chondrocyte degeneration, gene chip, cell experiment

CLC Number:

Xie Xiaochen, Yang Qi, Weng Jian, Zeng Hui, Kang Bin, Liu Pei, Zhong Huage, Yu Fei. Activation of chondrocyte degeneration related signaling pathways and expression of differential factors in ATDC5 mouse cells after silent information regulator 1 knockdown[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(32): 5112-5118.

Figures/Tables 13

References

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Activation of chondrocyte degeneration related signaling pathways and expression of differential factors in ATDC5 mouse cells after silent information regulator 1 knockdown

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