Human gingival tissue‐derived mesenchymal stem cells inhibit proliferation and invasion of rheumatoid fibroblast‐like synoviocytes via the CD39/CD73 signaling pathway
Abstract Background Gingiva‐derived mesenchymal stem cells (GMSCs) suppress immune and inflammatory responses in experimental arthritis models. Here, we determined whether GMSCs suppress the proliferation and invasion of rheumatoid arthritis fibroblast‐like synoviocytes (RA FLSs). Methods Surface ma...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-06-01
|
| Series: | Rheumatology & Autoimmunity |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rai2.12075 |
| _version_ | 1827913047250829312 |
|---|---|
| author | Weiqian Chen Ye Yu Song Guo Zheng Jin Lin |
| author_facet | Weiqian Chen Ye Yu Song Guo Zheng Jin Lin |
| author_sort | Weiqian Chen |
| collection | DOAJ |
| description | Abstract Background Gingiva‐derived mesenchymal stem cells (GMSCs) suppress immune and inflammatory responses in experimental arthritis models. Here, we determined whether GMSCs suppress the proliferation and invasion of rheumatoid arthritis fibroblast‐like synoviocytes (RA FLSs). Methods Surface markers of GMSCs were analyzed by flow cytometry. mRNA expression of matrix metalloproteinases and pro‐inflammatory cytokine in RA FLSs was measured by quantitative polymerase chain reaction (PCR). RA FLS proliferation was analyzed by a 5‐ethynyl‐2′‐deoxyuridine assay. To explore the molecular mechanisms, we assessed the effect of GMSCs on RA FLS proliferation by adding indoleamine‐2,3‐dioxygenase (IDO), CD39, or CD73 inhibitors. The invasion was analyzed by a transwell assay. The anti‐inflammatory effects of GMSCs were assessed in a type II collagen‐induced arthritis (CIA) mouse model. Results Compared with human dermal fibroblast, GMSCs displayed a higher expression of CD39. Interleukin (IL)‐8, IL‐6, MMP‐1, MMP‐3, MMP‐13, and monocyte chemoattractant protein‐1 mRNA were all decreased in RA FLSs after incubation with GMSCs. GMSCs significantly reduced RA FLS proliferation in a dose‐dependent manner in vitro, which was partly dependent on CD39/CD73 signaling. GMSCs significantly impeded the invasive capacity of RA FLSs in a dose‐dependent manner in vitro. GMSCs infusion delayed arthritis onset and reduced arthritis scores in the CIA model. Conclusion GMSCs are effective to inhibit the aggressive behavior of RA FLSs and treat experimental arthritis, implying their therapeutic potential in RA patients. |
| first_indexed | 2024-03-13T02:24:51Z |
| format | Article |
| id | doaj.art-2b565a46a24a43608a084bb97b8a2c3b |
| institution | Directory Open Access Journal |
| issn | 2767-1429 |
| language | English |
| last_indexed | 2024-03-13T02:24:51Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Rheumatology & Autoimmunity |
| spelling | doaj.art-2b565a46a24a43608a084bb97b8a2c3b2023-06-30T04:47:24ZengWileyRheumatology & Autoimmunity2767-14292023-06-0132909910.1002/rai2.12075Human gingival tissue‐derived mesenchymal stem cells inhibit proliferation and invasion of rheumatoid fibroblast‐like synoviocytes via the CD39/CD73 signaling pathwayWeiqian Chen0Ye Yu1Song Guo Zheng2Jin Lin3Division of Rheumatology, First Affiliated Hospital Zhejiang University School of Medicine Hangzhou ChinaDivision of Rheumatology, First Affiliated Hospital Zhejiang University School of Medicine Hangzhou ChinaDivision of Rheumatology, Department of Medicine Penn State University Hershey College of Medicine Hershey Pennsylvania USADivision of Rheumatology, First Affiliated Hospital Zhejiang University School of Medicine Hangzhou ChinaAbstract Background Gingiva‐derived mesenchymal stem cells (GMSCs) suppress immune and inflammatory responses in experimental arthritis models. Here, we determined whether GMSCs suppress the proliferation and invasion of rheumatoid arthritis fibroblast‐like synoviocytes (RA FLSs). Methods Surface markers of GMSCs were analyzed by flow cytometry. mRNA expression of matrix metalloproteinases and pro‐inflammatory cytokine in RA FLSs was measured by quantitative polymerase chain reaction (PCR). RA FLS proliferation was analyzed by a 5‐ethynyl‐2′‐deoxyuridine assay. To explore the molecular mechanisms, we assessed the effect of GMSCs on RA FLS proliferation by adding indoleamine‐2,3‐dioxygenase (IDO), CD39, or CD73 inhibitors. The invasion was analyzed by a transwell assay. The anti‐inflammatory effects of GMSCs were assessed in a type II collagen‐induced arthritis (CIA) mouse model. Results Compared with human dermal fibroblast, GMSCs displayed a higher expression of CD39. Interleukin (IL)‐8, IL‐6, MMP‐1, MMP‐3, MMP‐13, and monocyte chemoattractant protein‐1 mRNA were all decreased in RA FLSs after incubation with GMSCs. GMSCs significantly reduced RA FLS proliferation in a dose‐dependent manner in vitro, which was partly dependent on CD39/CD73 signaling. GMSCs significantly impeded the invasive capacity of RA FLSs in a dose‐dependent manner in vitro. GMSCs infusion delayed arthritis onset and reduced arthritis scores in the CIA model. Conclusion GMSCs are effective to inhibit the aggressive behavior of RA FLSs and treat experimental arthritis, implying their therapeutic potential in RA patients.https://doi.org/10.1002/rai2.12075Gingiva‐derived mesenchymal stem cellsrheumatoid arthritistype II collagen‐induced arthritis |
| spellingShingle | Weiqian Chen Ye Yu Song Guo Zheng Jin Lin Human gingival tissue‐derived mesenchymal stem cells inhibit proliferation and invasion of rheumatoid fibroblast‐like synoviocytes via the CD39/CD73 signaling pathway Rheumatology & Autoimmunity Gingiva‐derived mesenchymal stem cells rheumatoid arthritis type II collagen‐induced arthritis |
| title | Human gingival tissue‐derived mesenchymal stem cells inhibit proliferation and invasion of rheumatoid fibroblast‐like synoviocytes via the CD39/CD73 signaling pathway |
| title_full | Human gingival tissue‐derived mesenchymal stem cells inhibit proliferation and invasion of rheumatoid fibroblast‐like synoviocytes via the CD39/CD73 signaling pathway |
| title_fullStr | Human gingival tissue‐derived mesenchymal stem cells inhibit proliferation and invasion of rheumatoid fibroblast‐like synoviocytes via the CD39/CD73 signaling pathway |
| title_full_unstemmed | Human gingival tissue‐derived mesenchymal stem cells inhibit proliferation and invasion of rheumatoid fibroblast‐like synoviocytes via the CD39/CD73 signaling pathway |
| title_short | Human gingival tissue‐derived mesenchymal stem cells inhibit proliferation and invasion of rheumatoid fibroblast‐like synoviocytes via the CD39/CD73 signaling pathway |
| title_sort | human gingival tissue derived mesenchymal stem cells inhibit proliferation and invasion of rheumatoid fibroblast like synoviocytes via the cd39 cd73 signaling pathway |
| topic | Gingiva‐derived mesenchymal stem cells rheumatoid arthritis type II collagen‐induced arthritis |
| url | https://doi.org/10.1002/rai2.12075 |
| work_keys_str_mv | AT weiqianchen humangingivaltissuederivedmesenchymalstemcellsinhibitproliferationandinvasionofrheumatoidfibroblastlikesynoviocytesviathecd39cd73signalingpathway AT yeyu humangingivaltissuederivedmesenchymalstemcellsinhibitproliferationandinvasionofrheumatoidfibroblastlikesynoviocytesviathecd39cd73signalingpathway AT songguozheng humangingivaltissuederivedmesenchymalstemcellsinhibitproliferationandinvasionofrheumatoidfibroblastlikesynoviocytesviathecd39cd73signalingpathway AT jinlin humangingivaltissuederivedmesenchymalstemcellsinhibitproliferationandinvasionofrheumatoidfibroblastlikesynoviocytesviathecd39cd73signalingpathway |