Cargando…

Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis

Accumulating evidence suggests that synovitis is associated with osteoarthritic process. Macrophages play principal role in development of synovitis. Our earlier study suggests that interaction between cartilage fragments and macrophages exacerbates osteoarthritic process. However, molecular mechani...

Descripción completa

Detalles Bibliográficos
Autores principales: Hamasaki, Masanari, Terkawi, Mohamad Alaa, Onodera, Tomohiro, Tian, Yuan, Ebata, Taku, Matsumae, Gen, Alhasan, Hend, Takahashi, Daisuke, Iwasaki, Norimasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200748/
https://www.ncbi.nlm.nih.gov/pubmed/32371954
http://dx.doi.org/10.1038/s41598-020-64515-1
_version_ 1783529402474168320
author Hamasaki, Masanari
Terkawi, Mohamad Alaa
Onodera, Tomohiro
Tian, Yuan
Ebata, Taku
Matsumae, Gen
Alhasan, Hend
Takahashi, Daisuke
Iwasaki, Norimasa
author_facet Hamasaki, Masanari
Terkawi, Mohamad Alaa
Onodera, Tomohiro
Tian, Yuan
Ebata, Taku
Matsumae, Gen
Alhasan, Hend
Takahashi, Daisuke
Iwasaki, Norimasa
author_sort Hamasaki, Masanari
collection PubMed
description Accumulating evidence suggests that synovitis is associated with osteoarthritic process. Macrophages play principal role in development of synovitis. Our earlier study suggests that interaction between cartilage fragments and macrophages exacerbates osteoarthritic process. However, molecular mechanisms by which cartilage fragments trigger cellular responses remain to be investigated. Therefore, the current study aims at analyzing molecular response of macrophages to cartilage fragments. To this end, we analyzed the transcriptional profiling of murine macrophages exposed to cartilage fragments by RNA sequencing. A total 153 genes were differentially upregulated, and 105 genes were down-regulated in response to cartilage fragments. Bioinformatic analysis revealed that the most significantly enriched terms of the upregulated genes included scavenger receptor activity, integrin binding activity, TNF signaling, and toll-like receptor signaling. To further confirm our results, immunohistochemical staining was performed to detected regulated molecules in synovial tissues of OA patients. In consistence with RNA-seq results, MARCO, TLR2 and ITGα5 were mainly detected in the intima lining layer of synovial tissues. Moreover, blockade of TLR2 or ITGα5 but not Marco using specific antibody significantly reduced production of TNF-α in stimulated macrophages by cartilage fragments. Our data suggested that blocking TLR2 or ITGα5 might be promising therapeutic strategy for treating progressive osteoarthritis.
format Online
Article
Text
id pubmed-7200748
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-72007482020-05-12 Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis Hamasaki, Masanari Terkawi, Mohamad Alaa Onodera, Tomohiro Tian, Yuan Ebata, Taku Matsumae, Gen Alhasan, Hend Takahashi, Daisuke Iwasaki, Norimasa Sci Rep Article Accumulating evidence suggests that synovitis is associated with osteoarthritic process. Macrophages play principal role in development of synovitis. Our earlier study suggests that interaction between cartilage fragments and macrophages exacerbates osteoarthritic process. However, molecular mechanisms by which cartilage fragments trigger cellular responses remain to be investigated. Therefore, the current study aims at analyzing molecular response of macrophages to cartilage fragments. To this end, we analyzed the transcriptional profiling of murine macrophages exposed to cartilage fragments by RNA sequencing. A total 153 genes were differentially upregulated, and 105 genes were down-regulated in response to cartilage fragments. Bioinformatic analysis revealed that the most significantly enriched terms of the upregulated genes included scavenger receptor activity, integrin binding activity, TNF signaling, and toll-like receptor signaling. To further confirm our results, immunohistochemical staining was performed to detected regulated molecules in synovial tissues of OA patients. In consistence with RNA-seq results, MARCO, TLR2 and ITGα5 were mainly detected in the intima lining layer of synovial tissues. Moreover, blockade of TLR2 or ITGα5 but not Marco using specific antibody significantly reduced production of TNF-α in stimulated macrophages by cartilage fragments. Our data suggested that blocking TLR2 or ITGα5 might be promising therapeutic strategy for treating progressive osteoarthritis. Nature Publishing Group UK 2020-05-05 /pmc/articles/PMC7200748/ /pubmed/32371954 http://dx.doi.org/10.1038/s41598-020-64515-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hamasaki, Masanari
Terkawi, Mohamad Alaa
Onodera, Tomohiro
Tian, Yuan
Ebata, Taku
Matsumae, Gen
Alhasan, Hend
Takahashi, Daisuke
Iwasaki, Norimasa
Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis
title Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis
title_full Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis
title_fullStr Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis
title_full_unstemmed Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis
title_short Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis
title_sort transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200748/
https://www.ncbi.nlm.nih.gov/pubmed/32371954
http://dx.doi.org/10.1038/s41598-020-64515-1
work_keys_str_mv AT hamasakimasanari transcriptionalprofilingofmurinemacrophagesstimulatedwithcartilagefragmentsrevealedastrategyfortreatmentofprogressiveosteoarthritis
AT terkawimohamadalaa transcriptionalprofilingofmurinemacrophagesstimulatedwithcartilagefragmentsrevealedastrategyfortreatmentofprogressiveosteoarthritis
AT onoderatomohiro transcriptionalprofilingofmurinemacrophagesstimulatedwithcartilagefragmentsrevealedastrategyfortreatmentofprogressiveosteoarthritis
AT tianyuan transcriptionalprofilingofmurinemacrophagesstimulatedwithcartilagefragmentsrevealedastrategyfortreatmentofprogressiveosteoarthritis
AT ebatataku transcriptionalprofilingofmurinemacrophagesstimulatedwithcartilagefragmentsrevealedastrategyfortreatmentofprogressiveosteoarthritis
AT matsumaegen transcriptionalprofilingofmurinemacrophagesstimulatedwithcartilagefragmentsrevealedastrategyfortreatmentofprogressiveosteoarthritis
AT alhasanhend transcriptionalprofilingofmurinemacrophagesstimulatedwithcartilagefragmentsrevealedastrategyfortreatmentofprogressiveosteoarthritis
AT takahashidaisuke transcriptionalprofilingofmurinemacrophagesstimulatedwithcartilagefragmentsrevealedastrategyfortreatmentofprogressiveosteoarthritis
AT iwasakinorimasa transcriptionalprofilingofmurinemacrophagesstimulatedwithcartilagefragmentsrevealedastrategyfortreatmentofprogressiveosteoarthritis