Origins of fibroblasts in rheumatoid synovial tissues: Implications from organ fibrotic models

Abstract

Fibroblasts play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Accumulation of fibroblasts in the synovial tissues characterizes the pathology of RA. Understanding how fibroblasts accumulate could lead to discovery of new therapeutic targets in RA treatment, while current antirheumatic therapies still have problems in efficacy and safety. In this regard, several studies have revealed cellular origins of fibroblasts in fibrotic tissues in murine models of organ fibrosis. Some studies employed lineage tracing, which bring generally convincing results, using transgenic mice. They demonstrated that resident fibroblasts, pericytes, mesenchymal stem cells, epithelial cells, endothelial cells and bone-marrow-derived and circulating cells can be cellular origins of fibroblasts in organ fibrotic tissues. In this review, we summarize and discuss available evidence for the origins of fibroblasts accumulating in the arthritic synovial tissues and organ fibrotic tissues.

Keywords:

• Fibroblasts
• fibrosis
• origin
• rheumatoid arthritis

Conflict of interest

Hitoshi Kohsaka received consulting fees and/or speaking fees from Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc., and Teijin Pharma Limited. H.K. also received research grants from Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Astellas Pharma Inc., Novartis Pharma K.K., Takeda Pharmaceutical Company Limited., Eisai Co., Ltd., Pfizer Japan Inc., Chugai Pharmaceutical Co., Ltd., Teijin Pharma Limited, Ayumi Pharmaceutical Corporation, AbbVie GK, Japan Blood Products Organization, Eli Lilly Japan K.K., and Asahi Kasei Pharma Corporation. Yusuke Matsuo received speaking fees from Pfizer Japan Inc. Tetsuya Saito and Akio Yamamoto have no conflict of interest to declare.