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

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Title: Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis
Authors: Hamasaki, Masanari Browse this author
Terkawi, Mohamad Alaa Browse this author
Onodera, Tomohiro Browse this author →KAKEN DB
Tian, Yuan Browse this author
Ebata, Taku Browse this author
Matsumae, Gen Browse this author
Alhasan, Hend Browse this author
Takahashi, Daisuke Browse this author →KAKEN DB
Iwasaki, Norimasa Browse this author →KAKEN DB
Issue Date: 5-May-2020
Publisher: Nature Publishing Group
Journal Title: Scientific reports
Volume: 10
Issue: 1
Publisher DOI: 10.1038/s41598-020-64515-1
Abstract: 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 ITG alpha 5 were mainly detected in the intima lining layer of synovial tissues. Moreover, blockade of TLR2 or ITG alpha 5 but not Marco using specific antibody significantly reduced production of TNF-alpha in stimulated macrophages by cartilage fragments. Our data suggested that blocking TLR2 or ITG alpha 5 might be promising therapeutic strategy for treating progressive osteoarthritis.
Type: article
Appears in Collections:国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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