Table 3.

Selected gene or gene product expressed by FLS.

Marker	Fibroblast Specificity*	Pathologic Role in RAs	Ref
Surface proteins
FAP	Highly specific	95-kDa cell surface-bound type II transmembrane serine protease. Expressed by fibroblastic cells in the area of active tissue remodeling. Associated with myofibroblast phenotype of FLS. Co-localized with MMP-1, MMP-13, and CD44 splice variants.	Bauer et al. 2006
CDH11	Moderate specific	Overexpressed in the synovium of RA pannus, mainly at the synovial lining cells. Also expressed by osteoblasts. Regulates cell-to-cell contact between FLS Promotes invasive capacity of FLS Cadherin-11 deficient mice are resistant to inflammatory arthritis. Anti-cadherin-11 monoclonal antibody ameliorates arthritis in the K/BxN model.	Kiener et al. 2006 and 2009; Valencia et al, 2004; Noss et al. 2011; Lee et al.2007
THY-1 (CD90)	Moderate Specific	35-kDa cell-surface glycoprotein. Expressed on brain cells, fibroblasts, activated endothelial cells. Soluble Thy-1 is elevated at the local inflammatory sites (i.e. synovial fluid).	Saalbach et al. 1999
VCAM-1 (CD106)	Less specific	Expressed on FLS within the intimal layer of normal, osteoarthritis, and RA synovium. Regulates cell-to-cell contact between FLS and macrophages Mediates endothelial progenitor cells adhesion to FLS Neutralizing VCAM-1 antibody reduces adhesion endothelial progenitor cell to FLS.	Wilkinson et al. 1993; Siverman et al. 2007
CD44	Less specific	Mediates cell–cell adhesion and cell–matrix interactions. Implicated in cellular homing, tumor invasiveness, metastasis, and angiogenesis. Intracytoplasmic phosphorylated by MIF-CD74 signal transduction.	Yoo et al. 2016
ICAM-1 (CD54)	Non-specific	Expressed on endothelial cells and leukocytes. Mediates cell-to-cell contact between FLS and macrophages.	Krenn et al. 1997
DAF (CD55)	Non-specific	70-kDa GPI-anchored membrane protein and protect cells from complement-mediated damage. CD55 is also a cellular ligand for CD97. CD55-deficient mice have reduced arthritis.	Hock et al. 2010; Hamann et al. 1999
Intracellular proteins
GREM1	Highly specific	20.7 kDa protein belonging to the subfamily of bone morphogenetic protein antagonists. Expressed in rheumatoid FLS, synovial tissue, and synovial fluid Essential to survival, migration, and invasion of rheumatoid FLS	Han et al. 2016
UDPGD	Less specific	Expressed preferentially by intimal lining fibroblasts Reflects hyaluronan synthesis ability.

CDH11=Cadherin-11; DAF=decay-accelerating factor; FAP=Fibroblast activation protein; FLS=fibroblast like synoviocytes; GPI=glycosylphosphatidylinositol; GREM1=Gremlin1; ICAM-1=intracellular adhesion molecule-1; kDa=kiloDalton; MIF=migration inhibitory factor; MMP=matrix metalloproteinase; THY1= thymocyte differentiation antigen 1; UDPGD=Uridine diphospho-glucose 6-dehydrogenase; VCAM-1=vascular cell adhesion molecule-1;

^*Specificity was determined based on the number of cells and tissues that are significantly expressed in various tissues and cell types in Genotype-Tissue Expression (GTEx) database. See Supplementary Figure S2 for details.