RRC ID 71970
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)