期刊
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
卷 16, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13018-021-02260-5
关键词
C-Jun N-terminal kinase; Inflammation; Osteoarthritis; Secreted frizzled-related protein 5; Wnt5a
类别
资金
- Medical Science and Technology Development Foundation, Nanjing Department of Health [YKK17062]
Overexpression of SFRP5 in ATDC5 cells inhibits LPS-induced inflammation and apoptosis by repressing Wnt5a/JNK signaling. The inhibitory effect of SFRP5 on inflammation and apoptosis is weakened by overexpressing Wnt5a, suggesting that Wnt5a/JNK activation may play a role in mediating the protective actions of SFRP5.
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-alpha, IL-1 beta, 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.
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