Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways
The development of osteoarthritis (OA) is characterized by synovial inflammation and the upregulation of vascular cell adhesion molecule type 1 (VCAM-1) in human osteoarthritis synovial fibroblasts (OASFs). This increase in VCAM-1 expression promotes monocyte adhesion to OASFs. The adipokine resisti...
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MDPI AG
2020-06-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/6/1369 |
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| author | Wei-Cheng Chen Chih-Yang Lin Shu-Jui Kuo Shan-Chi Liu Yung-Chang Lu Yen-Ling Chen Shih-Wei Wang Chih-Hsin Tang |
| author_facet | Wei-Cheng Chen Chih-Yang Lin Shu-Jui Kuo Shan-Chi Liu Yung-Chang Lu Yen-Ling Chen Shih-Wei Wang Chih-Hsin Tang |
| author_sort | Wei-Cheng Chen |
| collection | DOAJ |
| description | The development of osteoarthritis (OA) is characterized by synovial inflammation and the upregulation of vascular cell adhesion molecule type 1 (VCAM-1) in human osteoarthritis synovial fibroblasts (OASFs). This increase in VCAM-1 expression promotes monocyte adhesion to OASFs. The adipokine resistin is known to promote the release of inflammatory cytokines during OA progression. In this study, we identified significantly higher levels of resistin and CD68 (a monocyte surface marker) expression in human OA tissue compared with in healthy control tissue. We also found that resistin enhances VCAM-1 expression in human OASFs and facilitates the adhesion of monocytes to OASFs. These effects were attenuated by inhibitors of PKCα, p38, and JNK; their respective siRNAs; and by a microRNA-381 (miR-381) mimic. In our anterior cruciate ligament transection (ACLT) rat model of OA, the inhibition of resistin activity prevented ACLT-induced damage to the OA rat cartilage and pathological changes in resistin and monocyte expression. We also found that resistin affects VCAM-1 expression and monocyte adhesion in human OASFs by inhibiting miR-381 synthesis via the PKCα, p38, and JNK signaling pathways. Our clarification of the crucial role played by resistin in the pathogenesis of OA may lead to more effective therapy that reduces OA inflammation. |
| first_indexed | 2024-03-10T19:26:42Z |
| format | Article |
| id | doaj.art-6272ea6fe53247c8b9097618ff7ccf69 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:26:42Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6272ea6fe53247c8b9097618ff7ccf692023-11-20T02:29:33ZengMDPI AGCells2073-44092020-06-0196136910.3390/cells9061369Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling PathwaysWei-Cheng Chen0Chih-Yang Lin1Shu-Jui Kuo2Shan-Chi Liu3Yung-Chang Lu4Yen-Ling Chen5Shih-Wei Wang6Chih-Hsin Tang7Department of Medicine, MacKay Medical College, New Taipei City 252, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City 252, TaiwanSchool of Medicine, China Medical University, Taichung 404, TaiwanDepartment of Medical Education and Research, China Medical University Beigang Hospital, Yunlin 651, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City 252, TaiwanDepartment of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City 252, TaiwanSchool of Medicine, China Medical University, Taichung 404, TaiwanThe development of osteoarthritis (OA) is characterized by synovial inflammation and the upregulation of vascular cell adhesion molecule type 1 (VCAM-1) in human osteoarthritis synovial fibroblasts (OASFs). This increase in VCAM-1 expression promotes monocyte adhesion to OASFs. The adipokine resistin is known to promote the release of inflammatory cytokines during OA progression. In this study, we identified significantly higher levels of resistin and CD68 (a monocyte surface marker) expression in human OA tissue compared with in healthy control tissue. We also found that resistin enhances VCAM-1 expression in human OASFs and facilitates the adhesion of monocytes to OASFs. These effects were attenuated by inhibitors of PKCα, p38, and JNK; their respective siRNAs; and by a microRNA-381 (miR-381) mimic. In our anterior cruciate ligament transection (ACLT) rat model of OA, the inhibition of resistin activity prevented ACLT-induced damage to the OA rat cartilage and pathological changes in resistin and monocyte expression. We also found that resistin affects VCAM-1 expression and monocyte adhesion in human OASFs by inhibiting miR-381 synthesis via the PKCα, p38, and JNK signaling pathways. Our clarification of the crucial role played by resistin in the pathogenesis of OA may lead to more effective therapy that reduces OA inflammation.https://www.mdpi.com/2073-4409/9/6/1369osteoarthritisresistinVCAM-1miR-381monocytes |
| spellingShingle | Wei-Cheng Chen Chih-Yang Lin Shu-Jui Kuo Shan-Chi Liu Yung-Chang Lu Yen-Ling Chen Shih-Wei Wang Chih-Hsin Tang Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways Cells osteoarthritis resistin VCAM-1 miR-381 monocytes |
| title | Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways |
| title_full | Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways |
| title_fullStr | Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways |
| title_full_unstemmed | Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways |
| title_short | Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways |
| title_sort | resistin enhances vcam 1 expression and monocyte adhesion in human osteoarthritis synovial fibroblasts by inhibiting mir 381 expression through the pkc p38 and jnk signaling pathways |
| topic | osteoarthritis resistin VCAM-1 miR-381 monocytes |
| url | https://www.mdpi.com/2073-4409/9/6/1369 |
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