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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Cheng-Yu Chen, Lih-Jyh Fuh, Chien-Chung Huang, Chin-Jung Hsu, Chen-Ming Su, Shan-Chi Liu, Yu-Min Lin, Chih-Hsin Tang
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
R
Q
Acceso en línea:https://doaj.org/article/b1731f79523741e69484cfde3b4217f7
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:b1731f79523741e69484cfde3b4217f7
record_format dspace
spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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
work_keys_str_mv AT chengyuchen enhancementofccl2expressionandmonocytemigrationbyccn1inosteoblaststhroughinhibitingmir518a5pimplicationofrheumatoidarthritistherapy
AT lihjyhfuh enhancementofccl2expressionandmonocytemigrationbyccn1inosteoblaststhroughinhibitingmir518a5pimplicationofrheumatoidarthritistherapy
AT chienchunghuang enhancementofccl2expressionandmonocytemigrationbyccn1inosteoblaststhroughinhibitingmir518a5pimplicationofrheumatoidarthritistherapy
AT chinjunghsu enhancementofccl2expressionandmonocytemigrationbyccn1inosteoblaststhroughinhibitingmir518a5pimplicationofrheumatoidarthritistherapy
AT chenmingsu enhancementofccl2expressionandmonocytemigrationbyccn1inosteoblaststhroughinhibitingmir518a5pimplicationofrheumatoidarthritistherapy
AT shanchiliu enhancementofccl2expressionandmonocytemigrationbyccn1inosteoblaststhroughinhibitingmir518a5pimplicationofrheumatoidarthritistherapy
AT yuminlin enhancementofccl2expressionandmonocytemigrationbyccn1inosteoblaststhroughinhibitingmir518a5pimplicationofrheumatoidarthritistherapy
AT chihhsintang enhancementofccl2expressionandmonocytemigrationbyccn1inosteoblaststhroughinhibitingmir518a5pimplicationofrheumatoidarthritistherapy
_version_ 1718385169117741056