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BMC Rheumatol. 2019 Dec 02;3:46. doi: 10.1186/s41927-019-0093-4. eCollection 2019.

Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis.

BMC rheumatology

Tue W Kragstrup, Dong H Sohn, Christin M Lepus, Kazuhiro Onuma, Qian Wang, William H Robinson, Jeremy Sokolove

Affiliations

  1. 1Department of Immunology and Rheumatology, Stanford University, Stanford, CA USA.
  2. 2VA Palo Alto Health Care System, Palo Alto, CA USA.
  3. 3Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, DK-8000 Aarhus C, Denmark.
  4. 4Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
  5. 5Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Republic of Korea.

PMID: 31819923 PMCID: PMC6886182 DOI: 10.1186/s41927-019-0093-4

Abstract

BACKGROUND: The pathophysiology of osteoarthritis (OA) involves wear and tear, and a state of low-grade inflammation. Tissue repair responses include transforming growth factor beta (TGFβ)-induced myofibroblast production of extracellular matrix. Fibronectins are an essential part of the extracellular matrix, and injection of fibronectin fragments into rabbit joints is a previously established animal model of OA. Fibronectin containing the ED-A domain is currently being used as drug delivery target in the development of anti-inflammatory drugs (e.g. Dekavil).

METHODS: In this study, samples of synovial membrane were obtained from patients with knee OA undergoing joint replacement surgery. Immunostaining for ED-A fibronectin and the myofibroblast marker alpha smooth muscle actin (αSMA) was performed on fibroblast-like synovial cells (FLS) and synovial membranes. RAW 264.7 macrophages were incubated with recombinant ED-A fibronectin.

RESULTS: The staining of ED-A fibronectin in OA FLS was increased by TGFβ but not by TNFα, lipopolysaccharide, or IL-6 (

CONCLUSIONS: The disease process in OA shares features with the chronic wound healing response. Our findings support utilizing ED-A fibronectin for drug delivery or therapeutic targeting to reduce pro-inflammatory responses in OA.

© The Author(s) 2019.

Keywords: Arthritis; Drug delivery; Fibronectin; Inflammation; Myofibroblast; Osteoarthritis; Synoviocyte; Synovitis

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

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