Abstract
BackgroundSecreted 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.MethodsATDC5 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.ResultsThe 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.ConclusionSFRP5 could alleviate LPS-induced ATDC5 cell inflammation and apoptosis; these actions may rely on repressing Wnt5a/JNK activation.
Highlights
Secreted frizzled-related protein 5 (SFRP5) is an endogenous inhibitor of Wnt5a, which has been implicated in anti-inflammatory response
SFRP5 is downregulated upon LPS stimulation in ATDC5 cells First of all, to determine whether SFRP5 could participate in LPS-triggered damage in ATDC5 cells, we compared the expression of SFRP5 in ATDC5 before and after increasing concentrations of LPS treatment
Overexpression of SFRP5 represses Wnt5a expression and phosphorylation of Jun N-terminal kinase (JNK) we measured the expression of Wnt5a and (p)JNK in response to SFRP5 overexpression
Summary
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. The apoptosis and inflammation of chondrocyte plays a key role in the progression of OA [6]. Previous studies unanimously reported that SFRP5 exerted an antiinflammatory effect by inhibiting the non-canonical Wnt5a/ c-Jun N-terminal kinase (JNK) signaling pathway, playing a key role in repressing the occurrence and development of various diseases including obesity, cardiovascular diseases, and diabetes [10, 11]. SFRP5 was found to diminish cardiac inflammation and protect the heart from ischemia/reperfusion injury via inactivating the non-canonical Wnt5a/ JNK signaling [12]. A previous study implicated that SFRP5 could suppress inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes through downregulating JNK [13]. The Wnt/JNK pathway has been extensively documented to be involved in the progression of OA [14, 15]
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