Drs. Alexander, Watt, and Sawaji contributed equally to this work.
Activin A is an anticatabolic autocrine cytokine in articular cartilage whose production is controlled by fibroblast growth factor 2 and NF-κB
Version of Record online: 29 OCT 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 56, Issue 11, pages 3715–3725, November 2007
How to Cite
Alexander, S., Watt, F., Sawaji, Y., Hermansson, M. and Saklatvala, J. (2007), Activin A is an anticatabolic autocrine cytokine in articular cartilage whose production is controlled by fibroblast growth factor 2 and NF-κB. Arthritis & Rheumatism, 56: 3715–3725. doi: 10.1002/art.22953
- Issue online: 29 OCT 2007
- Version of Record online: 29 OCT 2007
- Manuscript Accepted: 12 JUL 2007
- Manuscript Received: 16 MAR 2007
- Research fellowship from the Royal College of Surgeons, London
- Clinical research fellowship from the Wellcome Trust
- Arthritis Research Campaign, UK
Proteomic analysis has previously shown that activin A, a member of the transforming growth factor β family, is produced by human articular cartilage. This study was undertaken to investigate whether activin A affects cartilage matrix catabolism and how its production is regulated.
The effect of exogenous activin A on interleukin-1–induced aggrecanase-generated neoepitope production was assessed by Western blotting, using medium from human cartilage explants. Levels of activin A production were determined by enzyme-linked immunosorbent assay. For genes of interest, messenger RNA (mRNA) induction in cartilage explants or primary chondrocyte monolayers was assessed by reverse transcriptase–polymerase chain reaction. Activin A activity in cartilage explant medium was measured by incubating it with human dermal fibroblasts and determining the increase in phospho-Smad2 by Western blotting.
Activin A (1–10 ng/ml) suppressed aggrecanase-mediated cleavage of aggrecan in human articular cartilage. Activin A mRNA and protein secretion were induced by dissection and culture of human or porcine articular cartilage. This activin A was biologically active. Its production was due to an active cellular process and was enhanced in osteoarthritic (OA) tissue. Activin A production on dissection was reduced by 80% by the fibroblast growth factor (FGF) receptor inhibitor PD173074 and by 70% by the IKK inhibitor BMS345541.
Activin A is potentially an anticatabolic molecule in articular cartilage. Its expression is induced by wounding in an FGF-2– and NF-κB–dependent manner. OA cartilage produced more activin A than did normal cartilage in vitro.