Reference - Detail
RRC ID | 71970 |
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Author | Sun M, Wang W, Min L, Chen C, Li Q, Weng W. |
Title | Secreted frizzled-related protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway. |
Journal | J Orthop Surg Res |
Abstract |
BACKGROUND:Secreted frizzled-related protein 5 (SFRP5) is an endogenous inhibitor of Wnt5a (wingless-type family member 5a), which has been implicated in anti-inflammatory response. In this study, we aimed to investigate whether SFRP5 could protect chondrocytes against LPS-induced inflammation and apoptosis. METHODS:ATDC5 cells that overexpressed with SFRP5 or not were challenged with LPS to observe the effects of SFRP5 overexpression on LPS-triggered inflammation and apoptosis as well as Wnt5a/JNK activation. Wnt5a was elevated in ATDC5 cells in the presence of SFRP5 overexpression, to determine whether Wnt5a/JNK signaling was involved in the actions of SFRP5. RESULTS:The mRNA and protein levels of SFRP5 was significantly reduced by LPS in a concentration-dependent manner. Overexpression of SFRP5 in ATDC5 cells inhibited LPS-induced inflammation and apoptosis, as evidenced by decreased production of TNF-α, IL-1β, IL-6, and ROS, together with a reduced ratio of TUNEL-positive cells, a lower expression of Bax and cleaved caspase 3, but a higher expression of Bcl-2. Meanwhile, SFRP5 overexpression also repress Wnt5a and phosphorylated JNK expression. However, the overexpression of Wnt5a considerably weakened the inhibitory effect of SFRP5 on LPS-triggered inflammation and apoptosis. Besides, the level of Wnt5a and JNK phosphorylation, which was inhibited by SFRP5 overexpression, was also partially recovered by Wnt5a overexpression. CONCLUSION:SFRP5 could alleviate LPS-induced ATDC5 cell inflammation and apoptosis; these actions may rely on repressing Wnt5a/JNK activation. |
Volume | 16(1) |
Pages | 129 |
Published | 2021-2-11 |
DOI | 10.1186/s13018-021-02260-5 |
PII | 10.1186/s13018-021-02260-5 |
PMID | 33573682 |
PMC | PMC7877043 |
MeSH | Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism Adaptor Proteins, Signal Transducing / physiology* Animals Apoptosis / genetics* Cell Line Chondrocytes / pathology* Chondrocytes / physiology Gene Expression* Inflammation / genetics* JNK Mitogen-Activated Protein Kinases / metabolism* Lipopolysaccharides / adverse effects Mice Signal Transduction / genetics* Signal Transduction / physiology* Wnt-5a Protein / metabolism* |
IF | 1.777 |
Resource | |
Human and Animal Cells | ATDC5(RCB0565) |