Secreted frizzled-related protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway.

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.

• Authors: Minghui Sun, Weijun Wang, Lingtian Min, Cheng Chen, Qing Li, Wenjie Weng
• Journal: Journal of orthopaedic surgery and research (J Orthop Surg Res) Vol. 16 Issue 1 Pg. 129 (Feb 11 2021) ISSN: 1749-799X [Electronic] England
• PMID: 33573682 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Lipopolysaccharides
• Sfrp5 protein, mouse
• Wnt-5a Protein
• Wnt5a protein, mouse
• JNK Mitogen-Activated Protein Kinases

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism, physiology)
• Animals
• Apoptosis (genetics)
• Cell Line
• Chondrocytes (pathology, physiology)
• Gene Expression
• Inflammation (genetics)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Lipopolysaccharides (adverse effects)
• Mice
• Signal Transduction (genetics, physiology)
• Wnt-5a Protein (metabolism)