Dr. Malfait has received consulting fees, speaking fees, and/or honoraria from Pfizer and Allergan (less than $10,000 each). Rush University and the Hospital for Special Surgery have filed an international patent application for biomarkers in osteoarthritis;
Synovial fluid from patients with early osteoarthritis modulates fibroblast-like synoviocyte responses to Toll-like receptor 4 and Toll-like receptor 2 ligands via soluble CD14
Article first published online: 26 JUN 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 7, pages 2268–2277, July 2012
How to Cite
Nair, A., Kanda, V., Bush-Joseph, C., Verma, N., Chubinskaya, S., Mikecz, K., Glant, T. T., Malfait, A.-M., Crow, M. K., Spear, G. T., Finnegan, A. and Scanzello, C. R. (2012), Synovial fluid from patients with early osteoarthritis modulates fibroblast-like synoviocyte responses to Toll-like receptor 4 and Toll-like receptor 2 ligands via soluble CD14. Arthritis & Rheumatism, 64: 2268–2277. doi: 10.1002/art.34495
- Issue published online: 26 JUN 2012
- Article first published online: 26 JUN 2012
- Accepted manuscript online: 10 APR 2012 11:49AM EST
- Manuscript Accepted: 29 MAR 2012
- Manuscript Received: 17 MAY 2011
- NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grant Number: 1K08-AR-057859-01
- Rush Translational Sciences Consortium (New Investigator Award)
- American College of Rheumatology Research and Education Foundation
- Association of Specialty Professors
- Atlantic Philanthropies
- John A. Hartford Foundation (jointly funded Junior Career Development Award)
Synovial inflammation, a feature of both osteoarthritis (OA) and meniscal injury, is hypothesized to be triggered in part via stimulation of Toll-like receptors (TLRs). We undertook this study to test whether a TLR-2– or TLR-4–stimulating factor in synovial fluid (SF) from patients with early knee OA with meniscal injury could lead to inflammatory activation of synoviocytes.
SF was obtained from patients with early OA cartilage damage undergoing arthroscopic meniscal procedures. SF was used to stimulate primary cultures of fibroblast-like synoviocytes (FLS) and cell lines transfected with TLR-2 or TLR-4. SF was used either alone or in combination with a TLR-2 stimulus (palmitoyl-3-cysteine-serine-lysine-4 [Pam3CSK4]) or a TLR-4 stimulus (lipopolysaccharide [LPS]). In blocking experiments, SF was preincubated with anti-CD14 antibody.
SF from these patients did not stimulate interleukin-8 (IL-8) release from TLR transfectants. Compared with SF on its own, SF (at concentrations of 0.09–25%) in combination with TLR-2 or TLR-4 ligands resulted in significant augmentation of IL-8 release from both transfectants and primary FLS. Soluble CD14 (sCD14), a coreceptor for TLRs, was measured in SF from patients with early OA at levels comparable to those in patients with advanced OA and patients with rheumatoid arthritis. Blockade with anti-CD14 antibody abolished the ability of SF to augment IL-8 production in response to LPS, and diminished Pam3CSK4 responses.
SF augments FLS responses to TLR-2 and TLR-4 ligands. This effect was largely due to sCD14. Our results demonstrate that sCD14 in the setting of OA and meniscal injury sensitizes FLS to respond to inflammatory stimuli such as TLR ligands.