2. Academic Validation
  3. 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

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

  • Inflammopharmacology. 2021 Jun;29(3):695-704. doi: 10.1007/s10787-021-00814-x.
Shuya Wang 1,  Ali Mobasheri 2 3 4 5,  Yue Zhang 1,  Yanli Wang 1,  Tianqi Dai 1,  Zhiyi Zhang 6
Affiliations

Affiliations

  • 1 Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng St, Harbin, 150001, China.
  • 2 Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, China. ali.mobasheri@oulu.fi.
  • 3 Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, PO Box 5000, 90014, Oulu, Finland. ali.mobasheri@oulu.fi.
  • 4 Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, 08406, Vilnius, Lithuania. ali.mobasheri@oulu.fi.
  • 5 Department of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, 508 GA, Utrecht, The Netherlands. ali.mobasheri@oulu.fi.
  • 6 Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng St, Harbin, 150001, China. zhangzhiyi2014@163.com.
PMID: 34085175 DOI: 10.1007/s10787-021-00814-x
Abstract

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.

Keywords

Low-grade inflammation; NLRP3 inflammasome; Osteoarthritis (OA); Pyroptosis; Stromal cell-derived factor-1; Synoviocyte; Synovitis.

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