Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy
Abstract Cysteine-rich 61 (Cyr61 or CCN1), a secreted protein from the CCN family, is an important proinflammatory cytokine. Migration and infiltration of mononuclear cells to inflammatory sites play a critical role in the pathogenesis of rheumatoid arthritis (RA). Monocyte chemoattractant protein-1...
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oai:doaj.org-article:b1731f79523741e69484cfde3b4217f72021-12-02T16:05:58ZEnhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy10.1038/s41598-017-00513-02045-2322https://doaj.org/article/b1731f79523741e69484cfde3b4217f72017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00513-0https://doaj.org/toc/2045-2322Abstract Cysteine-rich 61 (Cyr61 or CCN1), a secreted protein from the CCN family, is an important proinflammatory cytokine. Migration and infiltration of mononuclear cells to inflammatory sites play a critical role in the pathogenesis of rheumatoid arthritis (RA). Monocyte chemoattractant protein-1 (MCP-1/CCL2) is the key chemokine that regulates migration and infiltration of monocytes. Here, we examined the role of CCN1 in monocyte migration, and CCL2 expression in osteoblasts. We found higher levels of CCN1 and CCL2 in synovial fluid from RA patients compared with levels from non-RA controls. We also found that the CCN1-induced increase in CCL2 expression is mediated by the MAPK signaling pathway and that miR-518a-5p expression was negatively regulated by CCN1 via the MAPK cascade. In contrast, inhibition of CCN1 expression with lentiviral vectors expressing short hairpin RNA ameliorated articular swelling, cartilage erosion, and infiltration of monocytes in the ankle joints of mice with collagen-induced arthritis. Our study describes how CCN1 promotes monocyte migration by upregulating CCL2 expression in osteoblasts in RA disease. CCN1 could serve as a potential target for RA treatment.Cheng-Yu ChenLih-Jyh FuhChien-Chung HuangChin-Jung HsuChen-Ming SuShan-Chi LiuYu-Min LinChih-Hsin TangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Cheng-Yu Chen Lih-Jyh Fuh Chien-Chung Huang Chin-Jung Hsu Chen-Ming Su Shan-Chi Liu Yu-Min Lin Chih-Hsin Tang Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy |
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Abstract Cysteine-rich 61 (Cyr61 or CCN1), a secreted protein from the CCN family, is an important proinflammatory cytokine. Migration and infiltration of mononuclear cells to inflammatory sites play a critical role in the pathogenesis of rheumatoid arthritis (RA). Monocyte chemoattractant protein-1 (MCP-1/CCL2) is the key chemokine that regulates migration and infiltration of monocytes. Here, we examined the role of CCN1 in monocyte migration, and CCL2 expression in osteoblasts. We found higher levels of CCN1 and CCL2 in synovial fluid from RA patients compared with levels from non-RA controls. We also found that the CCN1-induced increase in CCL2 expression is mediated by the MAPK signaling pathway and that miR-518a-5p expression was negatively regulated by CCN1 via the MAPK cascade. In contrast, inhibition of CCN1 expression with lentiviral vectors expressing short hairpin RNA ameliorated articular swelling, cartilage erosion, and infiltration of monocytes in the ankle joints of mice with collagen-induced arthritis. Our study describes how CCN1 promotes monocyte migration by upregulating CCL2 expression in osteoblasts in RA disease. CCN1 could serve as a potential target for RA treatment. |
format |
article |
author |
Cheng-Yu Chen Lih-Jyh Fuh Chien-Chung Huang Chin-Jung Hsu Chen-Ming Su Shan-Chi Liu Yu-Min Lin Chih-Hsin Tang |
author_facet |
Cheng-Yu Chen Lih-Jyh Fuh Chien-Chung Huang Chin-Jung Hsu Chen-Ming Su Shan-Chi Liu Yu-Min Lin Chih-Hsin Tang |
author_sort |
Cheng-Yu Chen |
title |
Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy |
title_short |
Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy |
title_full |
Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy |
title_fullStr |
Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy |
title_full_unstemmed |
Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy |
title_sort |
enhancement of ccl2 expression and monocyte migration by ccn1 in osteoblasts through inhibiting mir-518a-5p: implication of rheumatoid arthritis therapy |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/b1731f79523741e69484cfde3b4217f7 |
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