Wang, S., Mobasheri, A., Zhang, Y. et al. Exogenous stromal cell-derived factor-1 (SDF-1) suppresses the NLRP3 inflammasome and inhibits pyroptosis in synoviocytes from osteoarthritic joints via activation of the AMPK signaling pathway. Inflammopharmacol 29, 695–704 (2021). https://doi.org/10.1007/s10787-021-00814-x
Exogenous stromal cell-derived factor-1 (SDF-1) suppresses the NLRP3 inflammasome and inhibits pyroptosis in synoviocytes from osteoarthritic joints via activation of the AMPK signaling pathway
|Author:||Wang, Shuya1; Mobasheri, Ali2,3,4,5; Zhang, Yue1;|
1Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng St, Harbin, 150001, China
2Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, China
3Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, PO Box 5000, 90014, Oulu, Finland
4Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, 08406, Vilnius, Lithuania
5Department of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, 508 GA, Utrecht, The Netherlands
|Online Access:||PDF Full Text (PDF, 2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2021090845539
|Publish Date:|| 2021-09-08
Objective: NLRP3 inflammasome may play a key role in OA pathogenesis. Stromal cell-derived factor-1 (SDF-1) is a homeostatic CXC chemokine. Since the role of SDF-1 in OA has not been explored, this study aimed to examine the effect of SDF-1 on NLRP3 inflammasome and pyroptosis in synoviocytes from OA joints.
Materials and methods: Human synovium was obtained from OA patients for isolation of primary synoviocytes and a murine model of collagenase-induced OA was established for testing intra-articular injections of SDF-1. Immunoblotting assays were used to examine the effects and underlying mechanism of action of SDF-1 on NLRP3 inflammasome and synoviocyte pyroptosis in synoviocytes. Inhibitors of AMPK and PI3K–mTOR were utilized to investigate the key signaling pathways involved in SDF-1-mediated OA inflammasome formation and pyroptosis.
Results: Synoviocytes from OA joints exhibited significantly higher expression of NLRP3 inflammasome and biomarkers of synoviocyte pyroptosis relative to healthy individuals. This was confirmed in the collagenase-induced OA model, where OA synoviocytes had a significantly lower SDF-1 expression than healthy ones. SDF-1 treatment in synoviocytes of OA patients and collagenase-induced OA led to significant downregulation in the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers. Inhibition of the AMPK signaling pathway significantly suppressed the inhibitory effect of SDF-1 on NLRP3 inflammasome expression of OA synoviocytes. However, blocking the SDF-1-activated PI3K–mTOR signaling pathway could still suppress the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers.
Conclusions: SDF-1 ameliorates NLRP3 inflammasome and pyroptosis in OA synoviocytes through activation of the AMPK signaling pathway. Therefore, SDF-1 may be a novel therapeutic target for OA.
|Pages:||695 - 704|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
3121 General medicine, internal medicine and other clinical medicine
This work was supported by grants from the National Natural Science Foundation of China to Zhiyi Zhang (NSFC 81771749) and Yue Zhang (NSFC81771748), and partially by the First Affiliated Hospital of HMU Merit Review Frontiers grant to Shuya Wang (HYD2020YQ0008) and Health and Health Commission of Heilongjiang Province grant to Yanli Wang (2019-013). Ali Mobasheri is supported by financial support from the European Structural and Social Funds (ES Struktūrinės Paramos) through the Research Council of Lithuania (Lietuvos Mokslo Taryba) according to the activity ‘Improvement of researchers’ qualification by implementing world-class R&D projects’ of Measure No. 09.3.3-LMT-K-712 (grant application code: 09.3.3-LMT-K-712-01-0157, agreement No. DOTSUT-215) and the new funding program: Attracting Foreign Researchers for Research Implementation (2018-2022). Open access funding provided by University of Oulu including Oulu University Hospital.
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