Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus

Mohammed Talha Shekhani, Toni S. Forde, Altynai Adilbayeva, Mohamed Ramez, Askhat Myngbay, Yergali Bexeitov, Volkhard Lindner, Vyacheslav A. Adarichev

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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). Conclusion: 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.

Original languageEnglish
Article number171
JournalArthritis research & therapy
Volume18
Issue number1
DOIs
Publication statusPublished - Jul 19 2016

Fingerprint

Arthritis
Collagen
Fibroblasts
Rheumatoid Arthritis
Experimental Arthritis
Joints
Tunica Intima
Synovial Membrane
Stromal Cells
Synoviocytes
Cell Movement
Tail
Actins
Microscopy
Carcinogenesis
Enzyme-Linked Immunosorbent Assay
Macrophages
Bone and Bones
Messenger RNA
Antibodies

Keywords

  • Animal model
  • Cell motility
  • Rrheumatoid arthritis
  • Synoviocytes

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Shekhani, M. T., Forde, T. S., Adilbayeva, A., Ramez, M., Myngbay, A., Bexeitov, Y., ... Adarichev, V. A. (2016). Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus. Arthritis research & therapy, 18(1), [171]. https://doi.org/10.1186/s13075-016-1067-1

Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus. / Shekhani, Mohammed Talha; Forde, Toni S.; Adilbayeva, Altynai; Ramez, Mohamed; Myngbay, Askhat; Bexeitov, Yergali; Lindner, Volkhard; Adarichev, Vyacheslav A.

In: Arthritis research & therapy, Vol. 18, No. 1, 171, 19.07.2016.

Research output: Contribution to journalArticle

Shekhani, MT, Forde, TS, Adilbayeva, A, Ramez, M, Myngbay, A, Bexeitov, Y, Lindner, V & Adarichev, VA 2016, 'Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus', Arthritis research & therapy, vol. 18, no. 1, 171. https://doi.org/10.1186/s13075-016-1067-1
Shekhani, Mohammed Talha ; Forde, Toni S. ; Adilbayeva, Altynai ; Ramez, Mohamed ; Myngbay, Askhat ; Bexeitov, Yergali ; Lindner, Volkhard ; Adarichev, Vyacheslav A. / Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus. In: Arthritis research & therapy. 2016 ; Vol. 18, No. 1.
@article{70426717e7b241fb9f898e70bec9638f,
title = "Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus",
abstract = "Background: 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. Methods: 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. Results: 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). Conclusion: 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.",
keywords = "Animal model, Cell motility, Rrheumatoid arthritis, Synoviocytes",
author = "Shekhani, {Mohammed Talha} and Forde, {Toni S.} and Altynai Adilbayeva and Mohamed Ramez and Askhat Myngbay and Yergali Bexeitov and Volkhard Lindner and Adarichev, {Vyacheslav A.}",
year = "2016",
month = "7",
day = "19",
doi = "10.1186/s13075-016-1067-1",
language = "English",
volume = "18",
journal = "Arthritis research & therapy",
issn = "1478-6354",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus

AU - Shekhani, Mohammed Talha

AU - Forde, Toni S.

AU - Adilbayeva, Altynai

AU - Ramez, Mohamed

AU - Myngbay, Askhat

AU - Bexeitov, Yergali

AU - Lindner, Volkhard

AU - Adarichev, Vyacheslav A.

PY - 2016/7/19

Y1 - 2016/7/19

N2 - Background: 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. Methods: 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. Results: 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). Conclusion: 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.

AB - Background: 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. Methods: 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. Results: 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). Conclusion: 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.

KW - Animal model

KW - Cell motility

KW - Rrheumatoid arthritis

KW - Synoviocytes

UR - http://www.scopus.com/inward/record.url?scp=84978647054&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978647054&partnerID=8YFLogxK

U2 - 10.1186/s13075-016-1067-1

DO - 10.1186/s13075-016-1067-1

M3 - Article

VL - 18

JO - Arthritis research & therapy

JF - Arthritis research & therapy

SN - 1478-6354

IS - 1

M1 - 171

ER -