Dataset Information

Knockdown of TRIM8 Attenuates IL-1?-induced Inflammatory Response in Osteoarthritis Chondrocytes Through the Inactivation of NF-?B Pathway.

ABSTRACT: Osteoarthritis (OA) is a degenerative joint disease associated with inflammatory response. Tripartite motif 8 (TRIM8) is a member of TRIM family that has been found to regulate inflammation. The present study was aimed to evaluate the role of TRIM8 in OA chondrocytes. Our results showed that TRIM8 expression was significantly increased in interleukin 1 beta (IL-1?)-stimulated OA chondrocytes. To knock down the TRIM8 expression in chondrocytes, the chondrocytes were transfected with si-TRIM8. Knockdown of TRIM8 attenuated IL-1?-induced production of inflammatory mediators including nitric oxide and prostaglandin E2. The increased expression levels of inducible nitric oxide synthase and cyclooxygenase-2 in IL-1?-induced chondrocytes were suppressed by TRIM8 knockdown. The IL-1?-induced production of proinflammatory cytokines including TNF-? and IL-6 was significantly decreased after transfection with si-TRIM8. Besides, knockdown of TRIM8 mitigated the IL-1?-induced decrease in aggrecan and collagen-II proteins expression and increase in matrix-degrading enzymes in chondrocytes. Furthermore, TRIM8 knockdown prevented IL-1?-induced nuclear factor kappa B (NF-?B) activation in chondrocytes. Taken together, these findings indicated that knockdown of TRIM8 attenuates IL-1?-induced inflammatory response in OA chondrocytes through the inactivation of NF-?B pathway. Thus, targeting TRIM8 might provide therapeutic treatment for OA.

SUBMITTER: Liu R

PROVIDER: S-EPMC7563946 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Knockdown of TRIM8 Attenuates IL-1β-induced Inflammatory Response in Osteoarthritis Chondrocytes Through the Inactivation of NF-κB Pathway.

Liu Ruoxi R Wu Hao H Song Huanjin H

Cell transplantation 20200101

Osteoarthritis (OA) is a degenerative joint disease associated with inflammatory response. Tripartite motif 8 (TRIM8) is a member of TRIM family that has been found to regulate inflammation. The present study was aimed to evaluate the role of TRIM8 in OA chondrocytes. Our results showed that TRIM8 expression was significantly increased in interleukin 1 beta (IL-1β)-stimulated OA chondrocytes. To knock down the TRIM8 expression in chondrocytes, the chondrocytes were transfected with si-TRIM8. Kno ...[more]

PMID: 32757662

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Project description:Osteoarthritis (OA) is a common degenerative disease that is associated with the degradation of articular cartilage. Accumulating evidence has confirmed that LIM mineralization protein-1 (LMP-1) is an important agent of bone formation and has been shown to be osteoinductive in various types of disease. However, the underlying mechanisms of LMP-1 in the pathogenesis of OA remain unknown. The present study aimed to evaluate the role and potential mechanism of LMP-1 in IL-1β-stimulated OA chondrocytes. CHON-001 cells were transfected with pcDNA3.1-LMP-1, pcDNA3.1, negative control-small interfering (si)RNA or LMP-1 siRNA for 24 h and then induced by IL-1β for 12 h to establish an OA model in vitro. Cell viability, apoptosis and inflammatory cytokine (IL-6, IL-8 and TNF-α) release were assessed using MTT assay, ﬂow cytometry and ELISA, respectively. The expression levels of LMP-1, cleaved-caspase 3, phosphorylated (p)-p65, p65, p-JNK and JNK were analyzed using reverse transcription-quantitative PCR and western blotting. Overexpression of LMP-1 notably alleviated the IL-1β-induced inflammatory response in CHON-001 cells, as shown by increased cell viability, decreased apoptosis, suppressed expression of cleaved-caspase 3 and a decreased cleaved-caspase 3/caspase 3 ratio. Moreover, IL-1β-induced secretion of IL-6, IL-8 and TNF-α in CHON-001 cells; this was reversed by pcDNA3.1-LMP-1. However, knocking down LMP-1 expression exert opposite effects on the IL-1β-induced inflammatory response in CHON-001 cells, as evidenced by the decreased cell viability, increased apoptosis, enhanced expression of cleaved-caspase 3 and cleaved-caspase 3/caspase 3 ratio and enhanced secretion of IL-6, IL-8 and TNF-α observed. The present data demonstrated that LMP-1 siRNA notably inhibited LMP-1 expression, suppressed cell viability, promoted apoptosis and enhanced cleaved-caspase 3 expression and cleaved-caspase 3/caspase 3 ratio. In addition, LMP-1 siRNA promoted the release of inflammatory factors in CHON-001 cells. It was also found that pcDNA3.1-LMP-1 inhibited p-p65 and p-JNK expression, as well as decreasing the p-p65/p65 and p-JNK/JNK ratio. Nevertheless, there was no significant difference in the mRNA expression levels of p65 and JNK between the groups. Taken together, these findings indicated that overexpression of LMP-1 alleviated IL-1β-induced chondrocytes injury by regulating the NF-κB and MAPK/JNK pathways, suggesting that LMP-1 may be a valuable therapeutic agent for OA treatment.

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Dataset Information

Knockdown of TRIM8 Attenuates IL-1?-induced Inflammatory Response in Osteoarthritis Chondrocytes Through the Inactivation of NF-?B Pathway.

Publications

Knockdown of TRIM8 Attenuates IL-1β-induced Inflammatory Response in Osteoarthritis Chondrocytes Through the Inactivation of NF-κB Pathway.

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