title: Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus.
abstract: The formation of destructive hypercellular pannus is critical to joint damage in rheumatoid arthritis (RA). The collagen triple helix repeat containing 1 (CTHRC1) protein expressed by activated stromal cells of diverse origin has previously been implicated in tissue remodeling and carcinogenesis. We recently discovered that the synovial Cthrc1 mRNA directly correlates with arthritis severity in mice. This study characterizes the role of CTHRC1 in arthritic pannus formation.
  
  
  
  Synovial joints of mice with collagen antibody-induced arthritis (CAIA) and human RA-fibroblast-like synoviocytes (FLS) were immunostained for CTHRC1, FLS and macrophage-specific markers. CTHRC1 levels in plasma from patients with RA were measured using sandwich ELISA. The migratory response of fibroblasts was studied with a transwell migration assay and time-lapse microscopy. Velocity and directness of cell migration was analyzed by recording the trajectories of cells treated with rhCTHRC1.
  
  
  
  Immunohistochemical analysis of normal and inflamed synovium revealed highly inducible expression of CTHRC1 in arthritis (10.9-fold). At the tissue level, CTHRC1-expressing cells occupied the same niche as large fibroblast-like cells positive for α-smooth muscle actin (α-SMA) and cadherin 11 (CDH11). CTHRC1 was produced by activated FLS predominantly located at the synovial intimal lining and at the bone-pannus interface. Cultured RA-FLS expressed CDH11, α-SMA, and CTHRC1. Upon treatment with exogenous rhCTHRC1, embryonic fibroblasts and RA-FLS significantly increased migration velocity, directness, and cell length along the front-tail axis (1.4-fold, p < 0.01).
  
  
  
  CTHRC1 was established as a novel marker of activated synoviocytes in murine experimental arthritis and RA. The pro-migratory effect of CTHRC1 on synoviocytes is considered one of the mechanisms promoting hypercellularity of the arthritic pannus.
authors.affiliation: Albert Einstein College of Medicine, Departments of Medicine (Division of Rheumatology) and Microbiology & Immunology, Bronx, NY, 10461, USA.
authors.forename: Mohammed Talha
authors.initials: MT
authors.lastname: Shekhani
authors.affiliation: Albert Einstein College of Medicine, Departments of Medicine (Division of Rheumatology) and Microbiology & Immunology, Bronx, NY, 10461, USA.
authors.forename: Toni S
authors.initials: TS
authors.lastname: Forde
authors.affiliation: National Laboratory Astana, Astana, 010000, Kazakhstan.
authors.forename: Altynai
authors.initials: A
authors.lastname: Adilbayeva
authors.affiliation: Albert Einstein College of Medicine, Departments of Medicine (Division of Rheumatology) and Microbiology & Immunology, Bronx, NY, 10461, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ramez
authors.affiliation: National Laboratory Astana, Astana, 010000, Kazakhstan.
authors.forename: Askhat
authors.initials: A
authors.lastname: Myngbay
authors.affiliation: National Laboratory Astana, Astana, 010000, Kazakhstan.
authors.forename: Yergali
authors.initials: Y
authors.lastname: Bexeitov
authors.affiliation: Maine Medical Center Research Institute, Scarborough, ME, 04704, USA.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Lindner
authors.affiliation: Albert Einstein College of Medicine, Departments of Medicine (Division of Rheumatology) and Microbiology & Immunology, Bronx, NY, 10461, USA. VAdarichev@gmail.com.|National Laboratory Astana, Astana, 010000, Kazakhstan. VAdarichev@gmail.com.|Department of Biology, Nazarbayev University, School of Science and Technology, Astana, 010000, Kazakhstan. VAdarichev@gmail.com.
authors.forename: Vyacheslav A
authors.initials: VA
authors.lastname: Adarichev
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D002465:Cell Movement; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006097:Granulation Tissue; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D000070918:Synoviocytes / Q000378:metabolism
chemical_list: D015415:Biomarkers; C502426:CTHRC1 protein, human; C530500:Cthrc1 protein, mouse; D016326:Extracellular Matrix Proteins
keywords: Animal model; Cell motility; Rrheumatoid arthritis; Synoviocytes