Secreted frizzled-related protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway
| Autor: | Wei-jun Wang, Cheng Chen, Qing Li, Minghui Sun, Wenjie Weng, Lingtian Min |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine lcsh:Diseases of the musculoskeletal system Cell Gene Expression Secreted frizzled-related protein 5 Apoptosis Caspase 3 Inflammation Endogeny Wnt-5a Protein Cell Line Mice 03 medical and health sciences Chondrocytes 0302 clinical medicine lcsh:Orthopedic surgery Osteoarthritis Animals Medicine Orthopedics and Sports Medicine Adaptor Proteins Signal Transducing 030203 arthritis & rheumatology Messenger RNA business.industry JNK Mitogen-Activated Protein Kinases C-Jun N-terminal kinase Wnt5a Cell biology WNT5A body regions lcsh:RD701-811 030104 developmental biology medicine.anatomical_structure embryonic structures Phosphorylation Surgery sense organs medicine.symptom lcsh:RC925-935 business Research Article Signal Transduction |
| Zdroj: | Journal of Orthopaedic Surgery and Research, Vol 16, Iss 1, Pp 1-8 (2021) Journal of Orthopaedic Surgery and Research |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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